Background: Polycystic Ovary Syndrome (PCOS) is one of the most common causes of anovulatory infertility. Currently, clomiphene citrate (CC) is considered the first-line therapy for ovulation induction for women with PCOS and infertility. Aromatase inhibitors (AIs) have been introduced as a new treatment option that could challenge CC for ovulation induction. Aim of the Work: The present study was designed to compare the efficacy of combined aromatase inhibitor (Letrozole) with metformin versus CC with metformin in PCOS patients. Patients and Methods: This study was done on 100 documented PCOS cases. They were divided into two groups, The 1st group received CC 50 mg twice daily from the 3rd day of cycle for 5 days and repeated for 3 cycles with metformin 500 mg 3 times daily as an adjunct with CC and continued for 3 cycles. The 2nd group received aromatase inhibitor (Letrozole) 2.5 mg twice daily from 3rd day of cycle for 5 days and repeated for 3 cycles with metformin 500 mg 3 times daily as an adjunct with letrozole and continued for 3 cycles. These cases were followed up for three cycles by transvaginal ultrasound folliculometry to document ovulation (size and number of follicles). Results: The results of the present study revealed both lines of treatment were effective in treatment of PCOS patients, with slight favorability in letrozole group but without statistically significant difference founded between CC group and letrozole group as regard ovulation rate, number of follicles at the end of first, second or third cycles, or as regard the diameter of follicles, i.e., both regimens showed efficacy to the same extent. Conclusion: both CC and letrozole are equally effective in treatment of infertility in PCOS patients, when combined with metformin treatment.