BACKGROUND The association of metabolic syndrome with coronary artery disease (CAD) has been studied extensively. However, little is known about the effect of Framingham risk score (FRS) and metabolic syndrome components on the association of metabolic syndrome with angiographically significant CAD. Our aim was to investigate whether that relationship is influenced by individual's 10-year CAD risk profile as assessed by FRS. Furthermore, we sought to elucidate whether metabolic syndrome is associated with angiographically significant CAD independently of its individual components. METHODS We studied a consecutive sample of 150 patients undergoing coronary angiography for the evaluation of chest pain. Metabolic syndrome was defined according to the revised National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, and the 10-year CAD risk was estimated by the FRS. RESULTS Metabolic syndrome patients had a 2-fold higher CAD prevalence compared to those without metabolic syndrome [odds ratio (OR), 2.004; 95% confidence interval (CI), 1.029-3.905] but this finding was attenuated after adjustment for FRS (OR, 1.770; 95% CI, 0.872-3.594). Stratification of patients into three groups according to FRS revealed that metabolic syndrome predictive ability was confined in those being at <10% 10-year CAD risk. Including metabolic syndrome and its individual components into the same logistic regression model, only the glucose criterion was an independent predictor of angiographically significant CAD (OR, 4.137; 95% CI, 1.477-11.583). CONCLUSIONS Metabolic syndrome is an independent determinant of angiographically significant CAD only among those individuals at low 10-year risk for future coronary events. Individual components of the syndrome, such as impaired fasting glucose, have a stronger association with CAD than the syndrome as a whole.