Objective: To compare the effect of N-acetyl cysteine and metformin on hormonal profile (insulin and T) and ovulation rate in women with clomiphene citrate–resistant polycystic ovary syndrome. Design: Prospective randomized controlled study. Setting: Department of obstetrics and gynecology in a university hospital in Egypt. Patient(s): Sixty-one infertile women with clomiphene citrate–resistant polycystic ovary syndrome were assigned randomly to receive either metformin (1,500 mg/d) or N-acetyl cysteine (1.8 g/d) for 6 weeks. Hormonal profile was determined before and after the course of the treatment. Folliculometry was performed to assess ovulation. ½Q4 Intervention(s): ---. Main Outcome Measure(s): Ovulation rate and insulin and T changes. Result(s): In the metformin group, there was a significant decrease in the fasting glucose, fasting insulin, and total T. In the N-acetyl cysteine group, there was no significant difference in the fasting glucose or fasting insulin and there was a significant decrease in total T. There was no significant difference in the fasting glucose–fasting insulin ratio in both groups. In the metformin group, the rate of ovulation was 51.6% (16/31), vs. 6.7% (2/30) in the ½Q5 N-acetyl cysteine group, which was statistically significant. Conclusion(s): Metformin alone is an effective drug in inducing ovulation in clomiphene citrate–resistant polycystic ovary syndrome, whereas N-acetyl cysteine alone is not. Further large studies are required to confirm our results.