Background:Hyperhomocysteinemia plays an important role in the anovulation in infertile women suffering from polycystic ovary syndrome (PCOS). However, long-term metformin therapy elevated homocysteine (Hcy) concentration in these individuals. Inositol increases serum insulin levels and improves ovulation. The aim of this study was to compare the effect of metformin and inofolic on the level of serum Hcy and oxidative markers in the infertile patients with PCOS.Materials and Methods:Eighty PCOS infertile women undergoing in vitro fertilization in the Umm-al-Banin clinical center, Dezful, Iran from December 2018 to September 2019 were invited to participate in this double blind randomized clinical trial. They were divided into two groups; group A who received metformin (1000 mg twice/day) and folic acid (400 μg /day) and group B who used inofolic (inositol+ olic acid 200 μg twice/day) for 3 months.Results:The mean Hcy levels increased significantly by metformin (P=0.02), but not by inofolic. There was a decrease in the total antioxidant capacity (TAC) after metformin administration (P=0.01). In both groups, a significant increase in folic acid levels was observed after treatment (P=0.04). Also, no significant change in vitamin B12 and malondialdehyde levels was observed in both groups (P=0.08).Conclusion:These findings indicate an increase in the serum Hcy levels as well as a remarkable decrease in TAC following metformin treatment. Given the rise in blood Hcy in PCOS patients, inofolic and other medications containing inositol can be prescribed instead of metformin (registration number: IRCT20190508043516N1).