Topical tretinoin (0.05%) improves fine facial wrinkles, mottled hyperpigmentation, and tactile roughness, which improve the skin’s appearance. Efficacy appears to be dose dependent, but higher doses of tretinoin (ie, 0.1%) have demonstrated corresponding increases in cutaneous side effects occurring in the first few weeks of treatment. This study compared the bioequivalence of a newer tretinoin emollient cream 0.05% (tre-A) with the discontinued brand 0.05% formulation (tre-B) and vehicle in 420 participants with mild to moderate facial photoaging over 24 weeks. Both active formulations were effective in treating fine facial wrinkles (70.5%–74.4% success rate) and mottled hyperpigmentation (82.8%–88.0% success rate). Results for tre-A and tre-B were bioequivalent and significantly superior to vehicle (P<.001 and P≤.002, respectively). The majority of adverse events (AEs) were mild to moderate (94% [300/318]) and were not drug related (97% [308/318]).The newer tre-A formulation is now commercially available with the fragrance and quarternium-15 having been removed from the original formulation.