Background: Recent studies suggest that elevation of plasma homocysteine is a potentially modifiable risk factor for cardiovascular disease and death. The aim of this study was to evaluate a possible relationship between homocysteine levels on admission and mid-term outcome in patients with acute myocardial infarction (MI) after percutaneous coronary intervention (PCI). Methods: A total of 1,307 acute MI patients underwent PCI were included and followed up during 12 months period, and these patients were stratified into tertile groups according to the plasma homocysteine levels. The influence of cardiac risk factors, medications, angiographic findings, and interventional procedures were analyzed, and Cox proportional hazard analysis was used to determine the influence of plasma homocysteine levels on mid-term mortality. End points were cardiac death, recurrent MI, target lesion revascularization (TLR), and a composite of major adverse cardiac events (MACE). Results: Study populations were divided into three groups; group 1 (homocysteine <10.0 umol/l, n = 441), group 2 (homocysteine = 10.0-12.6 umol/l, n = 441), and group 3 (homocysteine >12.6 umol/l, n = 425). A meaningful relationship between homocysteine levels (tertiles) and freedom from MACE was not found (p = 0.837), but graded relationship between homocysteine levels and cardiac death was found (p = 0.009). After adjustment for potential confounders by Cox regression analysis, meaningful association between homocysteine levels and cardiac death was abolished. Conclusions: This study suggests that plasma homocysteine is not an independent predictor of mid-term MACE in acute MI patients underwent PCI.