Oral isotretinoin is effective in the clinical control of acne, but the relationship between this treatment and its psychosocial impact on the patient has not been completely clarified. The aim of this study was to determine if the use of oral isotretinoin in total accumulated doses of 120 mg/kg in a sample of 346 patients with moderate acne was useful in controlling symptoms of anxiety and/or depression and improving quality of life. A further objective was to ascertain the level of patient satisfaction with the treatment. After 30 weeks, there was a significant reduction in clinical symptoms (p < 0.001). The negative impact on quality of life, measured with the Dermatology Life Quality Index and the Health Survey Short-Form-36 (p < 0.001), showed a significant reduction, as did the Hospital Anxiety and Depression Scale scores for anxiety (p < 0.001) and depression (p < 0.005). At the end of the study, the mean level of patient satisfaction with improvement of symptoms was 84.4%.