Background: Homocysteine (Hcy) plays an important role in vascular function and Hcy level contributes to pathogenesis of ischemic stroke (IS). MTHFR gene polymorphism may have effects on IS risks by influencing the Hcy metabolic pathway. In the present study, a case–control study was designed to evaluate the relationship among MTHFR C677Tpolymorphism, plasma Hcy level, and susceptibility of IS in Chinese population. Methods: A total of 300 patients with IS and 261 matched control subjects were recruited. Plasma Hcy concentration was determined using enzymatic cycling assay. MTHFR C677T polymorphisms were genotyped by PCR-RFLP. Results: Compared with controls, the plasma Hcy level was significantly higher in the IS patients (P