Patients with metabolic syndrome (MS) are at increased risk of cardiovascular atherosclerosis. The aim of this study was to evaluate the impact of MS on cardiovascular prognosis in context with atherosclerotic burden. A total of 811 patients with coronary heart disease (CHD) were included and carotid and leg arteries were examined using sonographic methods. Patients with low (CHD only, n = 428, 52.8%) or high atherosclerotic burden (CHD and peripheral atherosclerosis, n=383, 47.2%) were compared. Patients with >or=3 of the following criteria: triglycerides>or=150 mg/dl, high-density lipoprotein cholesterol<40 mg/dl (men) and <50 mg/dl (women), body mass index>30 kg/m2, blood pressure>or=130/85 mm Hg, and fasting glucose>or=100 mg/dl were defined as having MS (n=349, 43.0%). Follow-up data (median 6.7 years) were available for 807 patients (99.5%), and 175 patients (21.7%) experienced cardiovascular events (myocardial infarction, death, and stroke). The presence of MS significantly increased cardiovascular events in patients with low and high atherosclerotic burden (low: MS yes 21.2%, MS no 12.9%, p=0.02; high: MS yes 34.3%, MS no 26.5%, p=0.01). MS could be identified as an independent predictor for cardiovascular events in all patients (hazard ratio 1.7, 95% confidence interval 1.3 to 2.3, p<0.0001, adjusted) and patients with high atherosclerotic burden in particular (hazard ratio 1.8, 95% confidence interval 1.2 to 2.6, p=0.005, adjusted). In conclusion, MS markedly worsens the long-term prognosis of patients with both low and high atherosclerotic burden. Moreover, patients with high atherosclerotic burden and MS should be considered a high-risk population and treated accordingly.