Objective: To compare clomiphene citrate with N-acetyl cysteine vs. clomiphene citrate alone for augmenting ovulation in management of unexplained infertility. Design: Prospective randomized double-blind controlled trial. Setting: Department of obstetrics and gynecology in a university medical faculty in Egypt. Patient(s): Four hundred four patients as a study group (clomiphene citrate plus N-acetyl cysteine group) and 400 patients as a control group (clomiphene citrate-alone group). All women had unexplained infertility. Intervention(s): Patients in the study group were treated with clomiphene citrate (50-mg tablets) twice per day and with N-acetyl cysteine (1,200 mg/d orally) for 5 days starting on day 2 of the cycle. Patients in the control group were treated with clomiphene citrated with sugar powder. Main Outcome Measure(s): The primary outcomes were number and size of growing follicles, serum E-2, serum P, and endometrial thickness. The secondary outcome was the occurrence of pregnancy. Result(s): There were no statistically significant differences between the two groups in the number of follicles sized > 18 mm, mean E-2 levels, serum P, or endometrial thickness. Pregnancy rate was comparable in both groups (22.2% vs. 27%). Miscarriage rate was comparable in both groups (6.7% in the study group vs. 7.4% in the control group). Conclusion(s): N-Acetyl cysteine is ineffective in inducing or augmenting ovulation in patients with unexplained infertility and cannot be recommended as an adjuvant to clomiphene citrate in such patients.