BACKGROUND: Being overweight, a constituent of the metabolic syndrome, is also an important contributing factor to the development of coronary artery disease in younger patients, compared with the older patient population. Owing to the above-mentioned fact, we sought to assess the association of the metabolic syndrome with premature coronary artery disease. METHODS: In an analytic cross-sectional study, 940 patients (553 women<or=55 years and 387 men<or=45 years), 637 with coronary artery disease and 303 without coronary artery disease, were evaluated. The extent of atherosclerosis was assessed with a clinical vessel score. Besides established coronary artery disease risk factors, all patients were evaluated for the presence of metabolic syndrome based on the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: The overall prevalences of metabolic syndrome and coronary artery disease were 56 and 67.8%, respectively. Metabolic syndrome prevalence was higher in women than in men (69.6 vs. 36.4%, P<0.001). The odds ratio of metabolic syndrome for premature coronary artery disease was 1.82 (95% confidence interval 1.17-2.82) after adjusting for age and multiple established coronary artery disease risk factors; the strength of this association varied by sex (2.17 in men vs. 1.22 in women). CONCLUSIONS: This study revealed a stronger association between metabolic syndrome and coronary artery disease in men<or=45 years than in women<or=55 years. It seems that endogenous estrogens may play a role in reducing the effects of metabolic syndrome-related risk and therefore in spite of higher prevalence of metabolic syndrome in young women, the effect of this syndrome on coronary artery disease is more dominant in young men.