Various common genotypes of the polymorphism 677 C-->T of the methylenetetrahydrofolate reductase enzyme result in lower activity of the enzyme and in a subsequent increase in homocysteine levels. Many studies have analyzed the connection between this polymorphism and the beginning of coronary artery disease. However, conclusions have been controversial, and evidence of a connection between this polymorphism and the prognosis of coronary artery disease has been poorly evaluated. This prospective study evaluated the prognostic relevance of genotype TT in a cohort of 155 patients admitted to our hospital for treatment of an acute coronary syndrome accompanied by evidence of coronary atherosclerosis on coronary angiography. We found that patients with the genotype TT had higher homocysteine levels than did patients with the CT and CC genotypes (15.72 +/- 6.92 micromol/L vs 12.11 +/- 5.40 micromol/L and 12.01 +/- 4.25 micromol/L, P=0.01). After a mean follow-up of 13.4 +/- 7.4 months, we observed similar rates of major adverse cardiovascular events (CC, 29%; CT, 22%; and TT, 25%) and cardiovascular death (CC, 11%; CT, 7%; and TT, 8%). No difference in cardiovascular-death-free survival (log-rank analysis, 0.81; P=0.66) or event-free survival (log-rank analysis, 0.76; P=0.68) was found. The presence of genotype TT was not an independent predictor of prognosis after multivariate analysis by means of the Cox regression survival model. In conclusion, the presence of the TT genotype of the 677 C-->T polymorphism of the methylenetetrahydrofolate reductase enzyme was not related to prognosis in patients admitted to the hospital after an acute coronary syndrome.