Objective: To evaluate the efficacy of Letrozole in induction of ovulation in cases of CC-resistant PCOS and to compare between Letrozole responders and non-responders. Design: Prospective trial in infertility patients treated with CC Setting: Benha University Hospital Clinic, Egypt. Patient(s): Forty-four infertile women with anovulatory PCOS who failed to ovulate with CC. Intervention(s): Letrozole was given in a dose of 2.5 mg/day from day 3 to day 7 of the menstrual cycle. When the dominant follicle reached a diameter > 18 mm, HCG 10.000 U was given and timed intercourse was advised. Main outcome measure(s): Occurrence of ovulation, endomertial thickness, cervical score & pregnancy rate Results: On the day of HCG administration, the mean number of follicles ≥ 18mm was 1.21, the mean endometrial thickness was 10.2 mm and cervical mucus score was 11.42. Ovulation occurred in 24 cases (54.6%) and pregnancy in 6 cases (25%). There was no significant difference between Letrozole responders and non-responders as regards the age, period of infertility, BMI, waist circumference, LH, FS H or LH/FSH ratio. Conclusion(s): Induction of ovulation with Letrozole in CC-resistant PCOS is not dependent on age, period of infertility, BMI, waist circumference, menstrual pattern, hirsutism, LH, FSH or LH/FSH ratio. Further studies are necessary to confirm these results