We assessed possible long-term side-effects of isotretinoin therapy in 720 patients who had received one or more courses of treatment, and had a mean follow-up period of 4.9 years (range 2?12 years). Most patients (442) had received a total cumulative dose of 120?200 mg/kg body weight. One hundred and sixty-two patients received a cumulative dose of <120 mg/kg body weight, and 116 received a cumulative dose <200 mg/kg. Fifty-two patients (7.2%) reported persistent symptoms during the follow-up period. No correlation was found between age, sex, cumulative dose, or number of courses of isotretinoin and occurrence of reported possible side-effects. The reported symptoms were predominantly musculoskeletal (2%) or mucocutaneous (4.8%), and were mild in all cases. Xeroderma, dry eye syndrome, arthralgia, and possible exacerbation of eczema, were considered to be infrequent but probable long-term side-effects. The findings of this study indicate that isotretinoin in the treatment of acne is a safe drug, with no serious long-term side-effects.