What does the research show about tretinoin and topical retinoids?

Tretinoin and topical retinoids

Topical retinoids cleared more acne than vehicle in many trials, with 16% to 21% clear or almost clear on adapalene against 9%. Tretinoin 0.02% to 0.05% improved fine sun-related wrinkles modestly over 24 weeks, and the weakest strengths did not. Redness, peeling and dryness affected most users. Tazarotene is contraindicated in pregnancy.

Add to Bio HackChecked 2026-11-13

Status: Tretinoin and tazarotene are prescription drugs in the US. Tretinoin is FDA-approved for acne (Retin-A) and, at 0.02% (Renova), as an add-on to sun protection for fine facial wrinkles. Tazarotene 0.1% cream is approved for acne and plaque psoriasis, and is contraindicated in pregnancy. Adapalene 0.3% gel is prescription, and adapalene 0.1% gel is sold over the counter for acne.
Also called: tretinoin, Retin-A, Retin-A Micro, Renova, Altreno, Atralin, all-trans retinoic acid, retinoic acid, adapalene, Differin, tazarotene, Tazorac, Arazlo, Fabior, trifarotene, Aklief, topical retinoids, tret
Taken for: acne, blackheads, clogged pores, wrinkles, fine lines, skin aging, sun damage, collagen, uneven skin tone, dark spots, preventing aging, smoother skin

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help4

StrongShown to clear more acne than vehicle, with 16% to 21% clear or almost clear at 12 weeks on adapalene against 9% on vehicle.Very common
StrongShown to improve fine sun-related wrinkles modestly at tretinoin 0.02% or stronger, with 10% moderately improved against 3% on vehicle. Weaker strengths did not differ from placebo.Very common
LimitedOne small trial found tretinoin 0.1% raised new collagen I formation 80% in sun-damaged forearm skin over 10 to 12 months, against a 14% fall on vehicle.
LimitedLimited evidence: one trial each found tazarotene improved moderate sun damage over placebo, and one trial found it similar to tretinoin 0.05%.

Reported risks7

ModerateShown to cause dry skin in 22% on adapalene 0.3% against 4.5% on vehicle. On tretinoin 0.02%, almost every user had local reactions and 4% stopped.Very common
ModerateMixed results: a meta-analysis found no rise in birth defects after topical retinoids in early pregnancy, while the tazarotene label lists pregnancy as a contraindication.How often is not known
LimitedThe labels warn of heightened sunburn susceptibility on topical retinoids. They give no rate.How often is not known
LimitedThe tazarotene label warns of added sun sensitivity with thiazide diuretics, tetracyclines, fluoroquinolones, phenothiazines and sulfonamides.How often is not known
LimitedCase reports: the adapalene label lists anaphylaxis, swelling of the face, eyelids and lips, and itching after approval. The tretinoin label calls true contact allergy rare.How often is not known
LimitedThe Renova label reports atypical skin cell changes and more elastic tissue damage in some patients using tretinoin 0.05% for longer than 48 weeks, of unknown significance.How often is not known
LimitedOne trial found more deaths on tretinoin 0.1% than vehicle in older veterans and stopped early. The authors judged a causal link unlikely.How often is not known

What people take it for, and what was found

Shown to help4

StrongVery common

Acne

Shown to clear more acne than vehicle, with 16% to 21% clear or almost clear at 12 weeks on adapalene against 9% on vehicle.

Compared with vehicle cream or gel [1][2][3][4]; antibiotics and other acne drugs in a network analysis [5]

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: In the adapalene label trial, 21% on 0.3% gel and 16% on 0.1% gel were rated clear or almost clear at 12 weeks against 9% on vehicle, and total lesions fell 45.3%, 41.8% and 33.7% [2]. In two tazarotene 0.1% cream trials, 18% and 20% had no or minimal acne against 11% and 6% on vehicle, and total lesions fell a median 44% and 42% against 24% and 21% [3]. A systematic review of 54 trials found topical retinoids superior to vehicle on global assessments [1]. A network meta-analysis of 221 trials found topical retinoids comparable to oral or topical antibiotics for inflammatory lesions, and ranked combinations of a topical retinoid, benzoyl peroxide and an antibiotic behind only oral isotretinoin [5]. Tazarotene 0.045% lotion raised treatment success against vehicle (OR 2.1) [4].
Population: 653 people aged 12 to 52 with mild to moderate acne [2]; 424 and 411 people aged 12 and over in two trials [3]; 54 trials from 2008 to 2018 [1]; 65,601 patients in 221 trials, mean age 20.4, median 12 weeks [5]; 6 phase 3 trials in moderate to severe acne [4].
Sources: [5], [1], [2], [3], [4]
Caveats: Most trials ran 12 weeks. Most people on the drug did not reach clear or almost clear skin in the label trials [2][3]. The network analysis abstract gives no effect size for retinoids against vehicle [5].

StrongVery common

Fine wrinkles from sun damage

Shown to improve fine sun-related wrinkles modestly at tretinoin 0.02% or stronger, with 10% moderately improved against 3% on vehicle. Weaker strengths did not differ from placebo.

Compared with vehicle cream, with sun protection in both arms [7][8][9]

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: In a Cochrane review, tretinoin cream at 0.02% or higher was superior to placebo for mild to severe photodamage of the face and forearms. Improvement on 0.05% cream at 24 weeks had a relative risk of 1.73 (95% CI 1.39 to 2.14). No effect was seen at 0.001% or 0.01%, and benefit and irritation both rose with strength [7]. A 2025 meta-analysis found tretinoin improved fine wrinkles over vehicle (MD 0.412, 95% CI 0.233 to 0.590) [8]. In the Renova 0.02% label trials, 60% on tretinoin improved at least minimally against 39% on vehicle, and 10% against 3% moderately, after 24 weeks [9].
Population: 8 tretinoin trials in a review of 30 [7]; 1,361 patients aged 29 to 76 in 8 trials, 16 weeks to 2 years [8]; 559 lightly pigmented adults in 4 trials [9].
Sources: [7], [8], [9]
Caveats: Losses to follow-up were high in most trials [7]. Only 2 of the 5 Renova trials on their own showed a benefit, and the label states the cream does not eliminate wrinkles or reverse photoaging. In 107 darkly pigmented adults, 29% improved on tretinoin against 43% on vehicle [9].

Limited

Collagen formation in sun-damaged skin

One small trial found tretinoin 0.1% raised new collagen I formation 80% in sun-damaged forearm skin over 10 to 12 months, against a 14% fall on vehicle.

Compared with vehicle cream [11]

The numbers and sources

Effect: Collagen I formation was 56% lower in sun-damaged skin than in sun-protected skin. Daily tretinoin 0.1% cream increased collagen I formation by 80%, against a 14% decrease on vehicle (P = 0.006), measured in skin biopsies [11].
Population: 29 adults with photodamaged forearm skin, 15 on tretinoin and 14 on vehicle, plus 26 healthy adults for the baseline comparison [11].
Sources: [11]
Caveats: One small trial measured a tissue marker, not appearance. The Renova label states adequate data have not shown increases in some other skin protein markers [9].

Limited

Tazarotene and adapalene for sun damage

Limited evidence: one trial each found tazarotene improved moderate sun damage over placebo, and one trial found it similar to tretinoin 0.05%.

Compared with placebo [7]; tretinoin 0.05% in one trial [7]

The numbers and sources

Effect: Tazarotene 0.01% to 0.1% improved moderate photodamage over placebo in one study, and one trial found tretinoin 0.05% equivalent to tazarotene 0.05% and 0.1%. Both caused skin irritation and redness [7].
Population: Adults with moderate photodamage of the face in single trials [7].
Sources: [7]
Caveats: One trial per comparison. No trial of adapalene for sun damage was found in the sources reviewed here.

Mixed results3

Moderate

Differences between topical retinoids for acne

Mixed results: adapalene 0.1% cleared acne about as well as tretinoin 0.025%, worked faster in week 1 and irritated skin less. Tretinoin and tazarotene did not differ.

Compared with tretinoin 0.025% gel [6]; each other, in trials reviewed [1]

The numbers and sources

Effect: Across five investigator-blinded trials, adapalene 0.1% gel matched tretinoin 0.025% gel in reducing total lesions, reduced inflammatory and total lesions more at week 1, and had greater local tolerability at every visit [6]. A systematic review found no significant difference in efficacy between tretinoin and tazarotene. Adverse events occurred in 62% on tretinoin 0.05% against 19% on adapalene 0.1% and 40% on adapalene 0.3% [1].
Population: 900 people with mild to moderate acne, 450 per drug [6]; 54 trials [1].
Sources: [6], [1]
Caveats: The 1998 analysis pooled the manufacturer's own adapalene trials, published and unpublished [6]. The adverse event comparison in [1] draws on separate trials, not one head-to-head study.

Moderate

Coarse wrinkles, dark spots and rough skin

Mixed results: a 2025 meta-analysis found tretinoin improved coarse wrinkles, but the Renova 0.02% trials did not show it for coarse wrinkles, pigment, roughness or sagging.

Compared with vehicle cream [8][9][10]

The numbers and sources

Effect: Tretinoin improved coarse wrinkles over vehicle (MD 0.245, 95% CI 0.119 to 0.370) [8]. A systematic review of 7 trials, using 0.025% and stronger for 3 to 24 months, reported improvement in wrinkling, mottled pigmentation, sallowness and sun spots in every study [10]. The Renova 0.02% label states no two of its five trials showed a benefit on coarse wrinkling, mottled hyperpigmentation, roughness or laxity [9].
Population: 1,361 patients in 8 trials [8]; 7 randomized trials, mostly in women [10]; 656 evaluable adults in 5 trials [9].
Sources: [8], [9], [10]
Caveats: The positive reviews included stronger concentrations than Renova's 0.02% [10]. Outcome scales differed between trials [10].

Limited

Tretinoin against other topical anti-aging products

Limited evidence: across 25 small studies, products such as retinol and retinaldehyde matched tretinoin in 13, beat it in 7 and fell short in 3, and irritated less.

Compared with other forms of vitamin A, such as retinol and retinaldehyde, and other cosmetic products [12]

The numbers and sources

Effect: In 25 studies comparing tretinoin with other topical products, the comparator gave better results in 7, equivalent results in 13 and poorer results in 3. Most studies found the comparator less irritating and better tolerated [12].
Population: 25 comparative studies to December 2023 [12].
Sources: [12]
Caveats: The review rated most studies poor quality or biased, and did not pool results [12].

Claimed, not studied in people1

Untested

Preventing skin aging in young skin without sun damage

Not studied in people. The idea rests on collagen gains seen in already sun-damaged skin, and no trial tested starting tretinoin early to prevent aging.

No study in people. This rests on how it acts in the body.

The numbers and sources

Effect: In sun-damaged human skin, tretinoin raised collagen I formation [11]. The trials of wrinkles enrolled adults who already had photodamage [7][8].
Population: Adults with existing photodamage [7][8][11]. No trial in young people without it was found.
Sources: [11], [7], [8]
Caveats: Restoring collagen in damaged skin does not show what happens when undamaged skin is treated for years.

Doses studied

The Retin-A label lists tretinoin cream at 0.025%, 0.05% and 0.1% and gel at 0.01% and 0.025%, applied once a day before bed [13]. The Renova label trials used 0.02% cream once a day in the evening for 24 weeks, with sun protection [9]. In the Cochrane review, 0.02% and stronger outperformed placebo for photodamage, while 0.001% and 0.01% did not [7]. The collagen trial used 0.1% cream daily for 10 to 12 months [11]. The acne trials used adapalene 0.1% or 0.3% gel once daily in the evening [2], and tazarotene 0.1% cream once daily in the evening [3], each for 12 weeks. The skin cancer prevention trial used tretinoin 0.1% twice daily for 1.5 to 5.5 years [14].

Risks

Reported risks6

ModerateVery common

Redness, peeling, dryness and stinging

Shown to cause dry skin in 22% on adapalene 0.3% against 4.5% on vehicle. On tretinoin 0.02%, almost every user had local reactions and 4% stopped.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: In the adapalene 0.3% trial, patient-reported dry skin occurred in 22.1% against 4.5% on vehicle and skin discomfort in 14% against 1.5%. Physicians rated mild scaling in 43.5% and moderate scaling in 18.6%, mostly early in treatment [2]. With tretinoin 0.02%, almost all patients reported peeling, dryness, burning, stinging, redness or itching. In 32% the irritation was severe, paused treatment or needed a mild steroid, 7% against under 1% on vehicle needed a steroid, and 4% stopped [9]. On tazarotene 0.1% cream, peeling, dry skin, redness and burning each occurred in 10% to 30% [3]. Benefit and irritation both rose with tretinoin strength [7].
Population: 258 on adapalene 0.3% and 134 on vehicle for 12 weeks [2]; 339 adults on tretinoin 0.02% in vehicle-controlled trials [9]; acne trial participants on tazarotene [3]; 30 trials [7].
Sources: [2], [9], [3], [7]
Caveats: Irritation was mostly mild to moderate and fell after the first weeks [2]. Rates differ by drug and strength [1].

LimitedHow often is not known

Sunburn and sun sensitivity

The labels warn of heightened sunburn susceptibility on topical retinoids. They give no rate.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The tretinoin labels warn of heightened susceptibility to sunlight and advise against use on sunburned skin [13][9]. The tazarotene label lists photosensitivity and risk of sunburn as a warning [3]. The over-the-counter adapalene label tells users to limit sun and tanning bed exposure [15].
Population: Labeling statements [3][13][9][15].
Sources: [13], [9], [3], [15]
Caveats: No trial rates are given.

LimitedHow often is not known

Use with other sun-sensitizing drugs

The tazarotene label warns of added sun sensitivity with thiazide diuretics, tetracyclines, fluoroquinolones, phenothiazines and sulfonamides.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The label advises caution in people also taking drugs known to cause photosensitivity, naming thiazides, tetracyclines, fluoroquinolones, phenothiazines and sulfonamides [3]. The tretinoin label advises caution with products containing sulfur, resorcinol or salicylic acid, and with strongly drying soaps and cosmetics [13].
Population: Labeling statements [3][13].
Sources: [3], [13]
Caveats: A predicted combined effect, with no rate given.

LimitedHow often is not known

Allergic reactions

Case reports: the adapalene label lists anaphylaxis, swelling of the face, eyelids and lips, and itching after approval. The tretinoin label calls true contact allergy rare.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Postmarketing reports with adapalene include anaphylaxis, angioedema, face and eyelid swelling, lip swelling and itching, some needing medical treatment [2]. The tretinoin label states true contact allergy is rarely encountered [13]. The tazarotene label lists hives among hypersensitivity reactions [3].
Population: Postmarketing reports [2][3]; labeling statement [13].
Sources: [2], [13], [3]
Caveats: Reports have no denominator.

LimitedHow often is not known

Cell changes with long-term use

The Renova label reports atypical skin cell changes and more elastic tissue damage in some patients using tretinoin 0.05% for longer than 48 weeks, of unknown significance.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The label states there is evidence of atypical changes in melanocytes and keratinocytes and of increased dermal elastosis in some patients treated with tretinoin 0.05% for longer than 48 weeks, and that daily use beyond 52 weeks has not been studied in controlled trials [9].
Population: Some patients treated longer than 48 weeks, number not given [9].
Sources: [9]
Caveats: The label gives no rate and calls the significance unknown.

LimitedHow often is not known

Deaths in one trial of older veterans

One trial found more deaths on tretinoin 0.1% than vehicle in older veterans and stopped early. The authors judged a causal link unlikely.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The Veterans Affairs trial of tretinoin 0.1% twice daily to the face and ears was stopped 6 months early because of excess deaths in the tretinoin group. After adjusting for imbalances in age, other illnesses and smoking, the difference remained significant. The authors observed an association but did not infer a cause [17].
Population: 1,131 veterans, mean age 71, followed 2 to 6 years [17].
Sources: [17]
Caveats: Death was not a planned outcome. The abstract gives no death counts. No other source here reports such a signal.
Why limited: This rests on one trial, of 1,131 people. Strength counts independent studies that agree, so one trial is limited at any size.

Mixed results1

ModerateStudied in pregnancyHow often is not known

Pregnancy

Mixed results: a meta-analysis found no rise in birth defects after topical retinoids in early pregnancy, while the tazarotene label lists pregnancy as a contraindication.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Across studies of 654 women exposed to topical retinoids in the first trimester and 1,375 unexposed, major congenital malformations (OR 1.22, 95% CI 0.65 to 2.29) and miscarriage (OR 1.02, 95% CI 0.64 to 1.63) did not differ significantly. The authors state the study had too little power to justify use in pregnancy [16]. The tazarotene label calls it teratogenic and contraindicated in pregnancy, and asks for a negative pregnancy test within 2 weeks before starting. Of 9 women exposed to tazarotene in trials, 8 delivered apparently healthy babies [3]. The Retin-A label reports 30 birth defect cases over two decades, five of them holoprosencephaly, with no causal link established [13].
Population: 654 exposed and 1,375 unexposed pregnant women [16]; trial participants and spontaneous reports [3][13].
Sources: [16], [3], [13]
Caveats: Small numbers. Case reports have no denominator [13].

Possible, not studied in people1

Untested

Skin tumors with ultraviolet light in mice

Not studied in people. Animal studies found tretinoin added to the skin tumor effect of high-dose ultraviolet light in mice.

No study in people. This rests on animal studies.

The numbers and sources

Effect: In hairless albino mice, and later in pigmented mice, tretinoin applied with carcinogenic doses of ultraviolet light enhanced tumor formation. In a 91-week mouse study at doses above the tolerated skin dose, some skin tumors and liver tumors appeared, within background rates for the strain [13].
Population: Mice (animal) [13].
Sources: [13]
Caveats: The label states the significance for humans is not clear. In a human trial, tretinoin did not change skin cancer rates (see Claims tested and not found) [14].

Claims tested and not found

That tretinoin prevents skin cancer. In 1,131 high-risk veterans randomized to tretinoin 0.1% or vehicle for 1.5 to 5.5 years, new basal cell carcinoma at 5 years was 53% against 54%, and invasive squamous cell carcinoma 28% against 31%, with no difference in actinic keratosis counts [14].
That very low strengths of tretinoin smooth wrinkles. Tretinoin 0.001% and 0.01% did not show the benefit seen at 0.02% and above [7].
That Renova 0.02% reverses photoaging. Its label trials did not show a benefit on coarse wrinkles, pigment, roughness or laxity, and in darkly pigmented adults fewer improved on tretinoin than on vehicle [9].

Sources

Kolli SS, Pecone D, Pona A, et al. Topical Retinoids in Acne Vulgaris: A Systematic Review. American Journal of Clinical Dermatology. 2019. https://doi.org/10.1007/s40257-019-00423-z
U.S. Food and Drug Administration. DIFFERIN (adapalene) gel 0.3%, prescribing information. 2024. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a0031324-92a6-4c11-90e2-c2818f7278ec
U.S. Food and Drug Administration. TAZORAC (tazarotene) cream, prescribing information. 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=021744d1-a6d7-4ad6-99c2-7187c24e64c6
Shergill M, Ali MU, Abu-Hilal M. Comparison of the Efficacy of Clascoterone, Trifarotene, and Tazarotene for the Treatment of Acne: A Systematic Literature Review and Meta-Analysis. Dermatology and Therapy. 2024. https://doi.org/10.1007/s13555-024-01175-3
Huang CY, Chang IJ, Bolick N, et al. Comparative Efficacy of Pharmacological Treatments for Acne Vulgaris: A Network Meta-Analysis of 221 Randomized Controlled Trials. Annals of Family Medicine. 2023. https://doi.org/10.1370/afm.2995
Cunliffe WJ, Poncet M, Loesche C, et al. A comparison of the efficacy and tolerability of adapalene 0.1% gel versus tretinoin 0.025% gel in patients with acne vulgaris: a meta-analysis of five randomized trials. British Journal of Dermatology. 1998. https://doi.org/10.1046/j.1365-2133.1998.1390s2048.x
Samuel M, Brooke RC, Hollis S, et al. Interventions for photodamaged skin. Cochrane Database of Systematic Reviews. 2005. https://doi.org/10.1002/14651858.CD001782.pub2
Huang HY, Lee LT. Tretinoin for Photodamaged Facial Skin: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Dermatology Practical & Conceptual. 2025. https://doi.org/10.5826/dpc.1504a5172
U.S. Food and Drug Administration. RENOVA (tretinoin cream) 0.02%, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f0a0e8d-1051-48a4-80c5-1bd260dd9c36
Sitohang IBS, Makes WI, Sandora N, et al. Topical tretinoin for treating photoaging: A systematic review of randomized controlled trials. International Journal of Women's Dermatology. 2022. https://doi.org/10.1097/JW9.0000000000000003
Griffiths CE, Russman AN, Majmudar G, et al. Restoration of Collagen Formation in Photodamaged Human Skin by Tretinoin (Retinoic Acid). New England Journal of Medicine. 1993. https://doi.org/10.1056/NEJM199308193290803
Siddiqui Z, Zufall A, Nash M, et al. Comparing Tretinoin to Other Topical Therapies in the Treatment of Skin Photoaging: A Systematic Review. American Journal of Clinical Dermatology. 2024. https://doi.org/10.1007/s40257-024-00893-w
U.S. Food and Drug Administration. RETIN-A (tretinoin) cream and gel, prescribing information. 2024. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9556d73d-c573-4e0a-9feb-764ce2d1107b
Weinstock MA, Bingham SF, DiGiovanna JJ, et al. Tretinoin and the Prevention of Keratinocyte Carcinoma (Basal and Squamous Cell Carcinoma of the Skin): A Veterans Affairs Randomized Chemoprevention Trial. Journal of Investigative Dermatology. 2012. https://doi.org/10.1038/jid.2011.483
U.S. Food and Drug Administration. DIFFERIN (adapalene) gel 0.1%, over-the-counter Drug Facts label. 2022. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0739d631-171b-42a8-bd55-0022b8df2d8a
Kaplan YC, Ozsarfati J, Etwel F, et al. Pregnancy outcomes following first-trimester exposure to topical retinoids: a systematic review and meta-analysis. British Journal of Dermatology. 2015. https://doi.org/10.1111/bjd.14053
Weinstock MA, Bingham SF, Lew RA, et al. Topical Tretinoin Therapy and All-Cause Mortality. Archives of Dermatology. 2009. https://doi.org/10.1001/archdermatol.2008.542

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