We evaluated the hypothesis that a common polymorphism of the methylenetetrahydrofolate reductase gene (C677T), which results in increased levels of plasma homocysteine, may be a putative risk factor for venous thromboembolism (VT). Sixty-five cases of VT and 130 controls, both identified within the framework of an epidemiologic survey on thrombophilia, the Vicenza Thrombophilia and Arteriosclerosis (VITA) Project, were genotyped for the mutation. No increased risk of VT was found in carriers of the mutation. We conclude that screening for the C677T mutation of the methylenetetrahydrofolate reductase gene should not be recommended in unselected patients with VT.