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Hyperhomocysteinemia is associated with atherothrombotic disease and venous thrombosis. A common cause of mild-to-moderate hyperhomocysteinemia is a C→T substitution at position 677 of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, a key enzyme in homocysteine (Hcy) metabolism. Several studies have addressed the potential associations among hyperhomocysteinemia, the MTHFR polymorphism, and cerebrovascular disease. Results of these studies conflict, perhaps because of variations in study design, sample size, entry criteria, and outcome measures. These authors performed a systematic review and meta-analysis of case-control and cohort studies published in English since 1966 that assessed the risk for arterial ischemic stroke and tr…