In view of these, our meta-analysis is the largest meta-analysis that used the robust statistical method and methodological quality to derive the precise conclusion regarding the relationship of MTHFR gene polymorphism at 677 positions with the risk of ischemic stroke. In the stratified analysis, the association was found to be higher in the Asian population (OR: 1.30, 95% CI: 1.22-1.39) as compared to the Caucasian population (OR: 1.23, 95% CI: 1.08-1.40). This evidence concerns the gene MTHFR and ischemic stroke.