Objective. Substances such as inositol and N-acetylcysteine (NAC) have been recently shown to be effective in treatment of PCOS patients. The aim of this prospective trial is to evaluate the efficacy of NAC + Inositol + folic acid on ovulation rate and menstrual regularity in PCOS patients with and without insulin resistance. Methods. Among the 91 PCOS patients treated with NAC + Inositol + folic, insulin resistance was present in 44 subjects (A) and absent in 47 (B). The primary endpoint was the ovulation rate/year, determined by menstrual diary, serum progesterone performed between 21° and 24° days, ultrasound findings of growth follicular or luteal cysts, and luteal ratio. HOMA-index assessment after 6 and 12 months of treatment was evaluated as secondary endpoint. Results. In both groups there was a significant increase in ovulation rate and no significant differences were found in the primary outcome between two groups. In group A, a significant reduction of HOMA-index was observed. Conclusions. The association NAC + Inositol + folic, regardless of insulin-resistance state, seems to improve ovarian function in PCOS patients. Therefore, inositol and NAC may have additional noninsulin-related mechanisms of action that allow achieving benefits also in those patients with negative HOMA-index.