Objectives: Different drugs are prescribed for the induction of ovulation in patients with polycystic ovary syndrome (PCOS). The aim of this study was to compare the effect of letrozole alone with letrozole plus N-acetyl cysteine (NAC) on the pregnancy rate in patients with PCOS. Materials and Methods: This clinical trial studyincluded317 patients with PCOS in the infertility clinic of Zahedan in 2018. Patients were randomly divided into letrozole and NAC plus letrozole groups. Then, several parameters were evaluated in both groups, including the pregnancy rate, number of follicles larger than 18 mm, endometrial thickness, and the endometrial pattern. Finally, data were analyzed using SPSS 25, and t-test and chi-square tests were used for statistical analysis. Results: The mean age of study participants was 28.5 ± 4.9 years old. The mean duration of infertility in the intervention group was 4.5 ± 3.8 years. The mean anti-Müllerian hormone and the mean endometrial thickness of patients in the intervention group were 4.4± 3.6 ng/mL and 7.6 ± 2.5 mm, respectively. Eventually, the pregnancy rate was 14.6% (n = 23) and 7.5% (n = 12) in the intervention and control groups, respectively (P = 0.046). Conclusions:The results of this search revealed that the number of follicles with the size of 18 mm in the control group was higher compared to the intervention group, but the fertility rate in patients with PCOS receiving letrozole plus N-acetylcysteine was significantly higher.