Little information is available regarding the clinical effect of metabolic syndrome (MS) or its combined effect with smoking on subsequent cardiac events after acute myocardial infarction (AMI). To examine whether MS independently predicts cardiac events (cardiac death and nonfatal reinfarction) and to assess the combined effect of MS and smoking on cardiac events after AMI, we studied 3,858 survivors of AMI registered in the Osaka Acute Coronary Insufficiency Study (OACIS). During a median follow-up of 725 days, the incidence of cardiac events was higher in patients with MS than in those without MS (p=0.021). After adjustment for baseline characteristics, MS was an independent predictor of cardiac events after AMI (hazard ratio [HR] 1.480, 95% confidence interval [CI] 1.128 to 1.942, p=0.005). Compared with patients who did not have MS and were nonsmokers, the adjusted HR for cardiac events was 2.868 (95% CI 1.573 to 5.227, p=0.001) in patients with MS who continued smoking after AMI. Cessation of smoking after AMI was associated with a significantly lower risk of cardiac events in patients with MS (HR 0.485, 95% CI 0.281 to 0.837, p=0.009) but not in patients without MS (HR 0.618, 95% CI 0.330 to 1.157, p=0.132). In conclusion, MS is independently associated with an increased risk of cardiac events after AMI. Smoking has an additive adverse effect on cardiac events after AMI, and cessation of smoking is beneficial and strongly recommended for AMI, especially in patients with MS.