Objective : Hyperhomocysteinemia has been proven to be an independent risk factor for stroke. The genetic mutation of methylenetetrahydrofolate reductase(MTHFR) elevates serum homocysteine level, but it still remains controversial whether the MTHFR gene mutation could be a predictor of ischemic stroke. Therefore, we studied if this genetic defect could cause ischemic stroke independently. Methods : We gathered ischemic stroke subjects and age, sex-matched controls. Age, gender, past medical history, smoking habit, serum homocysteine level, and the MTHFR genotype were recorded. General characteristics of ischemic stroke subjects were compared to the controls. We classified the stroke according to the related vessels(small and large artery infarction) and single lesion and multiple infraction. Relevant risk of the MTHFR genotype was evaluated in each stroke subtype with multiple logistic regression analysis. Results : When the controls were compared to the whole ischemic stroke, there was no specific difference except some medical histories. However, further analysis based on stroke subtypes showed important results. The small artery infarction group, multiple infraction group had significant odds ratio of the MTHFR TT genotype adjusted for age, gender, medical history and smoking habit. Conclusions : The MTHFR TT genotype is an independent risk factor for certain types of ischemic stroke, small artery infarction and multiple infarction.