Adapalene, sold under the brand name Differin among others, is a third-generation topical retinoid primarily used in the treatment of mild-moderate acne, and is also used off-label to treat keratosis pilaris as well as other skin conditions. Studies have found adapalene is as effective as other retinoids, while causing less irritation. It also has several advantages over other retinoids. The adapalene molecule is more stable compared to tretinoin and tazarotene, which leads to less concern for photodegradation. It is also chemically more stable compared to the other two retinoids, allowing it to be used in combination with benzoyl peroxide. Due to its effects on keratinocyte proliferation and differentiation, adapalene is superior to tretinoin for the treatment of comedonal acne and is often used as a first-line agent. The Swiss company Galderma developed adapalene.

Per the recommendations of the Global Alliance on Improving Outcomes of Acne, retinoids such as adapalene are considered first-line therapy in acne treatment and are to be used either independently or in conjunction with benzoyl peroxide and/or an antimicrobial agent, like clindamycin, for maximum efficacy. An adapalene/benzoyl peroxide combination medication is also available. Furthermore, adapalene, like other retinoids, increases the efficacy and penetration of other topical acne medications that are used in conjunction with topical retinoids as well as hastens the improvement of the postinflammatory hyperpigmentation caused by acne. In the long term, it can be used as maintenance therapy.

Adapalene has the unique ability to inhibit keratinocyte differentiation and decrease keratin deposition. This property makes adapalene an effective treatment for keratosis pilaris and callus. Other non-FDA approved indications that have been reported in the literature include treatment of warts, molluscum contagiosum, Darier's disease, photoaging, pigmentary disorders, actinic keratoses and alopecia areata.

While adapalene is sold at 0.1% in over-the-counter topical products for treatment of acne, its availability is otherwise restricted to prescription drugs. A version of adapalene, oleyl adapalenate, is available for broader skincare and cosmetic usage.

Of the three topical retinoids, adapalene is often regarded as the best tolerated. It can cause mild adverse effects such as photosensitivity, irritation, redness, dryness, itching, and burning, and 1% to 10% of users experience a brief sensation of warmth or stinging, as well as dry skin, peeling and redness during the first two to four weeks using the medication. These effects are considered mild and usually decrease over time. Serious allergic reactions are rare.

Use of topical adapalene in pregnancy has not been well studied but has a theoretical risk of retinoid embryopathy. Thus far, there is no evidence that the cream causes problems in the baby if used during pregnancy.

Topical adapalene has poor systemic absorption and results in low blood levels (less than 0.025 mcg/L) even after long term use, suggesting that there is low risk of harm for a nursing infant.

Adapalene has been shown to enhance the efficacy of topical clindamycin, although adverse effects are also increased. Application of adapalene gel to the skin 3–5 minutes before application of clindamycin enhances penetration of clindamycin into the skin, which may enhance the overall efficacy of the treatment as compared to clindamycin alone.