BACKGROUND Despite acne persisting into adulthood in up to 50% of the population, very few therapeutic studies have been performed in this age group. OBJECTIVE To assess the efficacy of 5 mg/day isotretinoin in adult acne. METHODS An investigator initiated, industry-sponsored, randomized, double-blind, placebo-controlled, parallel-group clinical study of isotretinoin 5 mg/day in the treatment of low-grade adult acne for 16 weeks followed by an open-label phase of 16 weeks. Group 1 received 32 weeks of 5 mg isotretinoin/day; Group 2 first received 16 weeks of placebo, followed by 16 weeks open-label 5 mg isotretinoin/day. Patients were followed for a further 10 weeks off treatment. The primary end-point was the difference in acne lesion count and disability score after 16 weeks isotretinoin compared to placebo. Secondary end-points included differences in these counts/scores after 32 weeks of isotretinoin compared to baseline, and after 10 weeks off treatment, compared to end of treatment (week 32). RESULTS There were highly significant differences (P < 0.0001) in acne lesion count, Dermatology Life Quality Index and self-assessment after 16 weeks of isotretinoin, compared to placebo (both per protocol and intention to treat). Acne lesions fell significantly, within 4 weeks of 5 mg isotretinoin/day (Group 1) and continued to fall during 32 weeks of treatment [acne lesion count (mean ± SD): 11.3 ± 8.1 (baseline), 3.6 ± 5.5 (week 16), 1.3 ± 3.1 (week 32), P < 0.0001)]. There was a similar significant reduction in acne lesion count in Group 2, but only from week 20, 4 weeks after starting open-label 5 mg isotretinoin. Adverse effects were minimal. CONCLUSIONS Isotretinoin 5 mg/day is effective in reducing the number of acne lesions, and improving patients dermatologic quality of life, with minimal adverse effects.