Aim and background: This study aims to estimate the proportion of infertile women with polycystic ovary syndrome (PCOS) who ovulated with Letrozole and to assess the factors determining the response to ovulation induction with letrozole. Methods: This prospective cohort study was conducted in 90 women with PCOS attending an infertility clinic in a tertiary care center in the Southern part of Kerala. Letrozole (2.5 mg) was given twice daily for 5 days from day 3 of cycles, and a follicular study was done with serial ultrasound till a dominant follicle of >18 mm had formed and then triggered with Inj. HCG. Ultrasound features of ovulation are documented. A subject is labeled as a non-responder if she has not ovulated/no dominant follicle till day 18 of the menstrual cycle. The proportion of ovulation is estimated. Factors affecting ovulation were studied, and statistical significance was assessed. Results: The ovulation rates in the current study were overall 65.6%, and among the 4 different phenotypes, 35.7%, 53.8%, 72.7%, and 89.5%, respectively. Factors such as age, BMI, type of infertility, duration of infertility, metformin treatment, comorbidities like diabetes, thyroid dysfunction, dyslipidemia, ovarian volume, and antral follicle count (AFC) were not affecting ovulation. Ovulation rates in those who had prior ovulation induction or ovarian drilling were lower compared to those who had not undergone treatment. Hypertensives had lower ovulation rates. Conclusion: Letrozole (2.5 mg) twice daily in PCOS has an ovulation rate of 65.6% with better ovulation rates in milder phenotypes. Hypertensives had reduced chances of ovulation. Other factors affecting the response to ovulation are prior history of ovulation induction and ovarian drilling. Clinical significance: This study sheds some light on patient selection for ovulation induction with letrozole. It will also help in counseling regarding the success rates of ovulation induction in PCOS patients.