Background: Spironolactone has been used for over 20 years as an antiandrogen in the treatment of acne and hirsutism. No long-term studies of the safety of spironolactone used in this manner have been published. We present a study of the long-term safety and tolerance of spironolactone in 91 women with acne who were followed for up to 8 years. Methods: A survey questionnaire was sent to 210 patients, and a comparison chart review of all patients to whom the survey was sent was made. Results: Ninety-one completed surveys were analyzed, comprising 506 person-years of followup and 200 person-years of spironolactone exposure. Mean treatment length was 28.5 months (range = 0.5–122 months). During the 8-year followup period, there were no cases of serious illness attributable to spironolactone use. Side effects were present in 59% and resulted in cessation of the drug in 15%. Diuretic effect and menstrual irregularities were the most common adverse effects. Conclusions: After 200 person-years of exposure to spironolactone and 506 person-years of followup over 8 years, no serious illnesses thought to be attributed to spironolactone were reported. The long-term use of spironolactone in the treatment of acne in women appears to be safe. Side effects, however, are common, although not usually a cause for stopping the drug.