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Background: Polycystic ovarian syndrome (PCOS) is among the important causes of infertility in young women. Premature luteinizing hormone (LH) surge (PLS) is one of its complications. PLS can reduce the quality of oocytes and therefore decrease the success of intrauterine insemination (IUI). Letrozole, a non-steroidal aromatase inhibitor, prevents LH surge. In this study, we aim to evaluate the effects of letrozole on preventing premature LH surge in clomiphene-resistant patients with PCOS undergoing IUI. Materials and Methods: In this randomized clinical trial, 131 patients who were developed with PCOS were selected for IUI cycle, divided into two groups randomly: control group (n=67) and letrozole group (n=64). Incidence of premature LH surge, pregnancy, abortion and ongoing pregnancy rate, endometrial thickness and number of follicles were measured in both groups. Results: No significant difference was seen between mean ages in the two groups; 11.9% of the control group and 21.9% of the letrozole group became pregnant (P =0.005); furthermore, premature LH surge was seen in 4.7% of the letrozole group and 8.9% of the control group (P =0.003). E2 and Endometrial thickness was higher in letrozole group; however, LH was significantly higher in the control group (P =0.026). Conclusion: Administration of letrozole in clomiphene-resistant patients with PCO undergoing IUI cycle can decrease the incidence of PLS. In addition, it can increase pregnancy rate significantly. Therefore, using letrozole is more reasonable in patients who have not responded to clomiphene or are hypersensitive. [GMJ.2015;4(3):104-11]