Objective: To compare clinical and metabolic profiles between N-acetylcysteine and l- carnitine among women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). Methods: A randomized trial at Zagazig University between January 2017 and March 2018. Women with CC-resistant PCOS were allocated randomly to receive CC plus N- acetylcysteine or CC plus l-carnitine. The primary outcome was clinical pregnancy rate; secondary outcomes were ovulation rate and metabolic changes. Results: Overall, 162 women completed the study (N-acetylcysteine group, n=82; l- carnitine group, n=80). After 3 months, there was no difference in pregnancy (P=0.15), ovulation (P=0.21), or spontaneous abortion (P=0.11) rates between the two groups. There was no significant decrease in BMI in either group (both P>0.05). There were improvements in menstrual pattern, follicle-stimulating hormone, luteinizing hormone, free testosterone, and insulin resistance markers in both groups (all P<0.05). An improvement in lipid profile was observed only in the l-carnitine group (P<0.001). N- Acetylcysteine treatment led to significantly greater improvement in free testosterone and insulin resistance parameters as compared with l-carnitine (all P<0.05). Conclusions: Both N-acetylcysteine and l-carnitine were equally effective in improving pregnancy and ovulation rates among women with CC-resistant PCOS. However, N- acetylcysteine was superior in ameliorating insulin resistance and only l-carnitine improved lipid profile.