Metabolic syndrome (MS) is highly prevalent and an established key risk factor for coronary artery disease, regardless of the presence or absence of diabetes mellitus (DM). Long-term follow-up studies have addressed the influence of MS with and without DM on the prognosis of patients undergoing percutaneous coronary intervention (PCI). We classified 748 consecutive patients who had undergone PCI into four groups as follows: neither DM nor MS, DM alone, MS alone, and both DM and MS. Post hoc analyses were conducted using prospectively collected clinical data. Multivariate Cox regression was used to evaluate the risk within each group for all-cause mortality and composite cardiac events (cardiac death, non-fatal acute coronary syndrome), adjusting for age, gender, body mass index, low-density lipoprotein (LDL) cholesterol level, hypertension, smoking, prior coronary artery bypass graft, presentation of acute coronary syndrome, left ventricular ejection fraction, multivessel disease, and procedural success. The progress of 321 (42.9%) patients with neither DM nor MS, 109 (14.6%) patients with DM alone, 129 (17.2%) patients with MS alone, and 189 (25.3%) patients with both DM and MS was followed up for a mean of 12.0+/-3.6 years. Patients with both DM and MS had significant risk for increased all-cause mortality (2.10 [1.19-3.70]). Patients with MS alone (2.14 [1.31-3.50]) and with both DM and MS (1.87 [1.18-2.96]) were at significant risk for increased cardiac events. In conclusion, the risk of cardiac events is significantly increased in patients with metabolic syndrome following PCI, irrespective of DM.