Objective: To evaluate the efficacy of combined therapy of letrozole and CC compared to the use of letrozole alone to achieve ovulation in infertile women with PCOS. Design: This was a single-centre, double arm, triple-blind randomized controlled trial. The study was conducted after taking approval from Institutional Ethics Committee and was prospectively registered with the clinical trials registry- India. Setting: Women were randomly assigned to receive a combination of 2.5 mg letrozole and placebo daily or a combination of 2.5 mg letrozole and 50 mg CC daily on cycle days 3–7 for one treatment cycle. Methods: 80 participants were enrolled and randomized to either the letrozole-only group (n=40) or the combined letrozole and CC group(n=40). Main outcome measures: The primary outcome measure was documentation of ovulation, confirmed by TVS 48 hours later with or without serum progesterone estimation.Results: In comparison, both Intention to treat (ITT) and per-protocol (PP) analysis showed a statistically significant increase in ovulation rate in the arm treated with combined letrozole and CC. Conclusion: Combination therapy with letrozole and clomipheneshould be considered as a first-line ovulation induction agent for infertile patients with PCOS owing to its low cost and better tolerability. Additional well designed clinical trials are required to determine the efficacy of the combination of letrozole and CC in terms of clinical pregnancy rates and live birth rates. Funding: There is no funding agency for this study. Keywords: Clomiphene, Letrozole, Polycystic ovarian syndrome, ovulation induction