Background: The purpose of the study was to evaluate the role of clinical, metabolic, hormonal and ultrasound features of women with PCOS in predicting the response to clomiphene citrate in treatment of infertility. Methods: A prospective observational study was done over a period of one year. A total of 164 women with PCOS related infertility were enrolled. They were treated with an incremental dose of clomiphene citrate starting with 50 mg/day to a maximum of 150 mg over 3 cycles. The response was recorded as either presence or absence of ovulation. Multiple logistic regression was used to analyze various clinical, metabolic, hormonal and ultrasound features in these women. Sensitivity and specificity of each of these parameters in predicting non-responsiveness (failure to ovulate with 150 mg clomiphene) were calculated. Results: Ferriman-Gallwey score, androstenedione levels, HDL, and cholesterol were found to be the independent predictors of non-responsiveness to clomiphene citrate. The overall best predictor of non-responsiveness to clomiphene citrate is Ferriman- Gallwey score (FG). FG score, with a cut off value of 15, had 73.9% sensitivity and 86.8% specificity in predicting non-responsiveness to clomiphene. BMI was the best anthropometric predictor of the non-responsiveness to clomiphene. Fasting insulin was the best metabolic predictor of the non-responsiveness to clomiphene. AFC was the best ovarian reserve marker as the predictor of the non-responsiveness to clomiphene (cut-off value of 11.75 with 73.9% sensitivity and 73.7% specificity). Conclusion: Ferriman-Gallwey score, androstenedione levels, and lipid profile are clinically useful parameters to predict which groups of PCOS women are unlikely to respond to clomiphene.