BACKGROUND: Treatment with clobetasol propionate 0.05% cream is effective against lichen sclerosus et atrophicus (LSA) of the vulva. OBJECTIVE: The purpose of this study was to retrospectively evaluate whether clinical and histologic responses to topical clobetasol can be accomplished in penile LSA. METHODS: A self-assessment questionnaire was obtained from 22 men with LSA, and a clinical examination was performed in 21 of them. Biopsy specimens from 15 cases were compared before and after treatment. RESULTS: Itching, burning, pain, dyspareunia, phimosis, and dysuria decreased significantly (P < .001 to .05) after 1 to 2 daily applications, for a mean of 7.1 weeks (2-16 weeks). Additional operation for phimosis was required in 6 of the 22 men. All histologic LSA criteria were significantly (P < .01 to .05) reduced after treatment. CONCLUSION: Topical treatment of penile LSA with clobetasol propionate represents a safe and effective therapy with no risk of epidermal atrophy but with some potential for triggering latent infections, most importantly human papillomavirus.