Objective: To evaluate the efficacy of combined therapy of letrozole and Clomiphene (CC) compared to the use of letrozole alone to achieve ovulation in infertile women with PCOS. Methods: This was a single-centre, double arm, triple-blind randomized controlled trial. The study was approved by Institutional Ethics Committee and was prospectively registered with the clinical trials registry- India. Participants were randomly assigned for ovulation induction with combination of 2.5 mg letrozole and placebo or a combination of 2.5 mg letrozole and 50 mg CC on cycle days 3–7 for one treatment cycle. Thus a total of 80 participants were included into either the letrozole and placebo group (n=40) or the combined letrozole and CC group (n=40). Results: Ovulation rate was found to be significantly higher in the arm treated with combined letrozole and CC according to Intention to treat (ITT) as well as per-protocol (PP) analysis. Conclusion: Combination therapy with letrozole and clomiphene should be considered as one of the first-line ovulation induction agents for infertile patients with PCOS owing to its low cost and better tolerability. Trial registration number: CTRI/2020/09/028012.