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Objective-We investigated the influence of elevated homocysteine plasma levels and 2 polymorphisms, 677C/T and 1298A/C, of the methylenetetrahydrofolate reductase (MTHFR) gene on the risk of restenosis after stenting in patients with symptomatic coronary artery disease. Methods and Results-Homocysteine levels and MTHFR genotypes were determined in 800 consecutive patients treated with coronary artery stenting. Angiographic restenosis (Ն50% diameter stenosis at 6-month follow-up) was present in 25.8% of the patients with low homocysteine levels (at or below the median of 11.6 mol/L; nϭ400) and 24.1% of the patients with high homocysteine levels (Ͼ11.6 mol/L; nϭ400; Pϭ0.62). Rates of angiographic restenosis were 26.0%, 23.5%, and 26.9% in carriers of the 677CC, 677CT, and 677TT genotypes (Pϭ0.75), respectively, and 24.4%, 25.9%, and 24.0% in patients with the 1298AA, 1298AC, and 1298CC genotypes (Pϭ0.90), respectively. The need for restenosis-driven reintervention (clinical restenosis) was 18.8% in subjects with low homocysteine concentrations and 19.0% in subjects with high homocysteine concentrations during the first year after the intervention (Pϭ0.93). Rates of clinical restenosis were 19.5%, 17.1%, and 23.3% in carriers of the 677CC, 677CT, and 677TT genotypes (Pϭ0.37), respectively, and 17.6%, 18.6%, and 24.7% in patients with the 1298AA, 1298AC, and 1298CC genotypes (Pϭ0.27), respectively. Conclusions-Elevated