Heart failure after acute myocardial infarction (AMI) is an important factor in determining clinical outcome. We examined whether the plasma homocysteine level was a predictor of heart failure in patients with AMI. A series of 96 patients without renal failure who were admitted to our hospital because of AMI between January 2003 and December 2005 were assigned to two groups; a group with a high homocysteine level (group H: n = 48) and a group with a low homocysteine level (group L: n = 48) based on a median homocysteine level. Congestive heart failure was defined as Killip Class II or higher at the time of admission or the development of congestive heart failure after hospitalization. The mean brain natriuretic peptide (BNP) level at the time of admission in group H was higher than that of group L (175.3 pg/mL versus 89.9 pg/mL; P = 0.068). The incidence of heart failure in group H was significantly higher than that in group L (43.7% versus 12.5%; P < 0.001, log-rank test; hazard ratio: 2.92). Multivariate Cox regression analysis indicated that a high plasma homocysteine level of 10.8 µmol/L or higher was a risk factor for the development of heart failure (HR: 7.175, P < 0.01). The plasma homocysteine level in patients with AMI may be related to the development of heart failure.