Background: For more than four decades clomiphene citrate has been the first line of the treatment for ovulatory disorders. The aim of this study was to compare the effects of letrozole and clomiphene citrate on ovulation and pregnancy rate in patients with polycystic ovary syndrome. Methods: In this prospective double-blind study, 100 patients with polycystic ovary syndrome were randomized into two equal groups. The first group received letrozole, 5mg daily (per oral) and the second group received clomiphene, 100mg daily during the 3rd-7th days of the menstrual cycles. Intramuscular human chorionic gonadotropin (hCG) (10,000 IU) was administered to trigger ovulation when at least one mature follicle (≥ 18mm) was developed. Results: Ovulation occurred in 30 patients (60%) of the letrozole group and in 16 patients (32%) of the clomiphene group, which showed a statistically significant difference (P=0.009). The mean number of follicles with diameter >14 mm on the day of administration of hCG was 1.06±0.95 in the letrozole group and 1.14±1.17 in the clomiphene group, which showed non-significant difference (P=0.962).No difference was found in the endometrial thickness between the two groups. A non-significant increase in pregnancy rate was observed in the letrozole group (26% v 14% P=0.21). Conclusion: Ovulation rate was higher in letrozole group and administration of letrozole was associated with a non-significant increase in pregnancy rate.