BACKGROUND: The efficacy of isotretinoin at 0.5 to 1.0 mg/kg per day in the treatment of acne is well established and considered safe, although it is sometimes not easily tolerated because of its cutaneous side effects. OBJECTIVE: The purpose of this study was to determine the efficacy of low-dose isotretinoin in the treatment of acne. METHODS: In this prospective, noncomparative, open-label study, 638 patients, both male and female, with moderate acne were enrolled and treated with isotretinoin at 20 mg/d (approximately 0.3-0.4 mg/kg per day) for 6 months. The patients were divided into two age groups: 12 to 20 and 21 to 35 years old. Patients were evaluated at 2-month intervals by means of clinical and laboratory examinations. A 4-year follow-up was also carried out. RESULTS: At the end of the treatment phase, good results were observed in 94.8% of the patients aged 12 to 20 years, and in 92.6% of the patients aged 21 to 35 years. Failure of the treatment occurred in 5.2% and 7.4% of the two groups, respectively. Twenty-one patients dropped out of the study because of lack of compliance, and another patient discontinued participation because of a laboratory side effect. During the 4-year follow-up period, relapses of the acne occurred in 3.9% of the patients aged 12 to 20 years and in 5.9% of the patients aged 21 to 35 years. Elevated serum lipid levels (up to 20% higher than the upper limit of normal value) were found in 4.2% of the patients and abnormal (<twice the upper limit of normal values) liver tests were observed in 4.8%. LIMITATIONS: This was a noncomparative, open-label study. CONCLUSION: Six months of treatment with low-dose isotretinoin (20 mg/d) was found to be effective in the treatment of moderate acne, with a low incidence of severe side effects and at a lower cost than higher doses.