IntroductionTopical tretinoin is considered the gold standard to treat photoaged skin, but it is associated with side effects and only available upon prescription. Aim of the studyTo compare the efficacy, tolerance, and perception of a fixed proprietary combination (Retinol 0.2%/LR2412 2%) vs. tretinoin 0.025% cream in women with photoaged skin. Material/MethodsIn this randomized, parallel, double-blind, controlled clinical study, women applied to the entire face for 3months in the morning a SPF 50 sunscreen and in the evening either the association of Retinol 0.2%/LR2412 2% or tretinoin 0.025%. Clinical and instrumental parameters were assessed at days 0, 28, 56, and 84. Subject perception of the efficacy, tolerance and cosmeticity of the tested products were assessed at days 28, 56, and 84. ResultsA total of 120 women (60 to Retinol 0.2%/LR2412 2% cream and 60 to tretinoin 0.025% cream) were included in the study. Both products improved considerably wrinkles, mottled pigmentation, pores, and global photodamage. No statistically significant differences were noted between Retinol 0.2%/LR2412 2% cream and tretinoin 0.025% cream. Adverse effects were mostly graded mild. Overall, Retinol 0.2%/LR2412 2% cream was better tolerated than tretinoin 0.025% cream. At all visits, subject perception of the association of Retinol 0.2%/LR2412 2% was either comparable to or better than tretinoin 0.025% cream. ConclusionThe treatment outcome of Retinol 0.2%/LR2412 2% cream does not differ from the one of tretinoin 0.025% cream. Clinical results were not statistically different. Furthermore, Retinol 0.2%/LR2412 2% cream is better tolerated and better perceived by women used to rejuvenation procedures.