Objective To compare the effects of Metformin with N-acetyl cysteine in polycystic ovarian syndrome (PCOS). Methods A prospective, randomised controlled study was conducted in the Department of Obstetrics and Gynaecology in a Medical College and General Hospital. Total 115 cases of polycystic ovarian syndrome presenting with different complaints were selected for the study. Fifty nine cases were treated with Metformin (Group-M) and other 56 with N-acetyl cysteine (Group-N). Primary outcome measures are improvement in clinical features and biochemical profile, where as secondary outcome measures are improvement in hormonal profile and ultrasonographic findings. Statistical analysis was done by Z test and Chi square test. Results From each group, 50 patients were ultimately evaluated. There was significant improvement in some of the clinical features like weight gain, acne and hirsutism in group-N (P < 0.05), but there was no significant change in other features like oligomenorrhea, amenorrhoea and infertility. The biochemical markers of insulin resistance like fasting insulin, fasting glucose/insulin ratio and HOMA-IR were significantly reduced in group-N. Hormone levels like serum LH, FSH, TT and LH/FSH ratio was significantly decreased in group-N, but FT, FT/TT ratio and SHBG were similar in both the groups. Ultrasonographic findings were similar in both the groups. Conclusion N-acetyl Cysteine had better improvement in clinical, biochemical and hormonal profile than Metformin in PCOS patients. It can be used as a substitute for insulin reducing medications in treatment of PCOS patients, considering its limited adverse effects.