The aim of this study was to evaluate the efficacy of co-administration of tamoxifen and letrozole as a novel protocol to increase pregnancy rates in ovulation induction. A trial conducted among 171 infertile women who were eligible for ovulation induction. Women randomized into two groups. Group A given letrozole 2.5 mg tablet daily and tamoxifen 10 mg twice daily started from the 3rd day of menstrual cycle for 5 days while for patients in group B letrozole only used. When at least one dominant follicle found, Human Chorionic Gonadotropin injection administrated intramuscularly. After 24 hours of the timed intercourse, all patients received vaginal progesterone daily. The mean number of mature follicles ≥ 18 mm was significantly higher in group A (2.6 ± 0.3 ) when compared to group B (1.5 ± 0.7 ) .Endometrial thickness was higher in group A (8.9 ± 1.4 mm versus 7.3 ± 1.2 mm in group B). As regarding pregnancy rate and ongoing pregnancy rate (21 and 19 % respectively) in-group A while (8 and 7 % respectively) in group B. Co-administration of tamoxifen with letrozole has valuable effect on increasing endometrial thickness resulted in increased pregnancy rates.