Background: Ovulatory dysfunction accounts for 20-25% of the cases of infertility. The main treatment modality for anovulatory infertility is ovarian stimulation. Clomiphene citrate (CC) and letrozole (LET) are the drugs of choice but which is the best choice for first line treatment is debatable.Objective: Compare the treatment outcome of anovulatory infertility by CC and LET.Method: A prospective randomized controlled trial including two groups of anovulatory subfertile patients was carried out at a tertiary care center and patients were randomized to either CC 50 mg (n=127) which was the standard first line treatment used at the center as the control and LET 2.5 mg (n=121) as the trial drug which is the off labelled, yet currently prescribed for the anovulatory sub-fertile patients daily from the 2nd to 6th day of the menstrual cycle. Follicle number on day 12, endometrial thickness, pregnancy rates and multiple pregnancies were assessed. The data were analyzed using MINITAB 14. Results:The mature follicles count (>18mm) on day 12 was not significantly different in two treatment groups (CC: 1.323± 0.935 and LET: 1.175±0.797). However, the mean endometrial thickness of the LET treated patients was significantly higher than the CC group (0.7691±0.0887 cm and 0.695± 0.134cm respectively). The clinical pregnancy rate of the LET group was significantly higher than the CC treated group (49% vs. 38%). There was no significant difference in the miscarriage rates (16% in both arms).Conclusions: LET treatment enhances the endometrial thickness compared to CC with higher clinical and ongoing pregnancy rates. The higher pregnancy rates with LET may be due to its favorable effects on endometrial thickness and the receptivity owing to its less anti-estrogenic properties