BACKGROUND: Risk of photocarcinogenesis and the relevance of collagen in wrinkle effacement are two issues related to prolonged use of retinoic acid (RA) that have not been fully addressed. OBJECTIVE: Our purpose was to investigate the degree of epidermal cellular atypia and the thickness of papillary dermal collagen in photoaging after long-term use of RA. METHODS: Thirty-four subjects with photoaged skin were treated daily with 0.05% RA for at least 6 months. Epidermal cellular atypia was graded by means of a semiquantitative scale. Thickness of collagen band was measured by using image-analysis software. RESULTS: Compared with pretreatment findings, melanocytic and keratinocytic atypia was significantly reduced and the collagen band thickness doubled. LIMITATIONS: This was an open-label study. CONCLUSION: Improvement in epidermal cellular atypia is consistent with the ability of RA to act as a chemopreventive agent in epithelial carcinogenesis. Prolonged use also significantly increased collagen matrix deposition in dermal repair zones, which most likely contributes to wrinkle effacement by RA.