Background: There are no well-established predictors of recurrent ischemic coronary events after an acute coronary syndrome (ACS). Higher levels of homocysteine have been reported to be associated with an increased atherosclerotic burden. The primary endpoint was to assess the relationship between homocysteine at discharge and very long-term recurrent myocardial infarction (MI). Methods: 1306 consecutive patients with ACS were evaluated (862 with non-ST-segment elevation ACS [NSTEACS] and 444 with ST-segment elevation myocardial infarction [STEMI]) discharged from October 2000 to June 2003 in a single teaching-center. The relationship between homocysteine at discharge and recurrent MI was evaluated through bivariate negative binomial regression accounting for mortality as a competitive event. Results: The mean age was 66.8 ± 12.4 years, 69.1% were men, and 32.2% showed prior diabetes mellitus. Most of the patients were admitted for an NSTEACS (66.0%). The median (interquartile range) GRACE risk score, Charlson comorbidity index, and homocysteine were 144 (122–175) points, 1 (1–2) points, and 11.9 (9.3–15.6) μmol/L, respectively. In-hospital revascularization was performed in 26.3% of patients. At a median follow-up of 9.7 (4.5–15.1) years, 709 (54.3%) deaths were registered and 779 recurrent MI in 478 (36.6%) patients. The rates of recurrent MI were higher in patients in the upper homocysteine quartiles (p < 0.001). After a multivariate adjustment, homocysteine along its continuum remained almost linearly associated with a higher risk of recurrent MI (p = 0.001) and all-cause mortality (p < 0.001). Conclusions: In patients with ACS, higher homocysteine levels identified those at a higher risk of recurrent MI at very long-term follow-up.