Background: Monotherapy is not usually effective in the treatment of hirsutism. Objective: Comparison of 2 therapeutic regimens in the treatment of hirsutism. Patients and methods: In this open parallel controlled clinical trial, 101 Patients suffering from hirsutism were randomly divided into two equal groups. 50 patients were treated with spironolactone (50 mg/day) plus cyproterone compound (From 5th to 26th day of menstrual cycle) and the other group (51 patients) received cyproterone acetate 50 mg/day (From 5th to 14th day of menstrual cycle) in addition to the above mentioned drugs for 6 months. The serum level of sex hormones and hirsutism score (Ferriman-Gallway) were determined before and after treatment. T-test, chi-2 test and linear regression analysis were used for data analysis. Results: Mean hirsutism score was 22.12±0.34 in first group and 22.15±0.34 in second group before treatment. Hirsutism score was reduced to 12.74±0.32 after treatment with 3 drugs and reduced to 16.73±0.35 after treatment with 2 drugs. This reduction was significantly more in the first group after adjustment for other confounding variables (P<0.001). Conclusion: These two therapeutic regimens were both effective in the treatment of hirsutism without serious hepatic, renal and metabolic side effects. Treatment with 3 anti-androgen drugs was more effective in reduction of hirsutism scores.