Background: Super ovulation and Intrauterine insemination is an effective treatment for infertile couples. Probability of pregnancy is increased by increasing the number of oocytes available and by correcting any subtle defects of ovulation. Clomiphene citrate has been the first line of treatment for subfertile couples for quite some time. Letrozole also has been successfully used for the ovulation induction and in contrast to Clomiphene Citrate, it does not deplete the estrogen receptors. Objective of this study is to compare Letrozole 2.5 mg and Clomiphene Citrate 100 mg as first line ovulation induction drug in sub-fertile women. Methods: 126 Treatment naive sub-fertile women were randomized to treatment with 2.5 mg Letrozole (63 Patients) or 100 mg Clomiphene Citrate (63 Patients) daily starting day 2 to 6 of menstrual cycle. Intra Uterine Insemination (IUI) was carried out 36 to 40 hrs after Human Chorionic Gonadotrophin (HCG) injection. Ovulation rate, endometrial thickness, pregnancy rate were compared and analyzed. Results: The groups were randomized so that the mean Body Mass Index (BMI), age and duration of infertility in both the groups were similar. Ovulation rate was 66.67% (42/63) in Letrozole group and 74.60% (47/63) in Clomiphene group. The median endometrial thickness on the day of hCG showed no significant difference between Letrozole group and clomiphene group. It was 8.1mm. Pregnancy rate in the Letrozole group was 9.52% (6/63) and in the Clomiphene group was 7.94% (5/63). Conclusion: No significant difference was seen between clomiphene citrate and letrozole as both have a comparable clinical pregnancy rate. However, letrozole has the advantage of development of fewer follicles; hence it may reduce the risk of multiple pregnancies.