Several evidences revealed the relationship between the earliest stages of atherosclerosis and the components of metabolic syndrome. The aim of this study was to disclose preclinical atherosclerotic lesions in a cross-sectional observational study involving 147 patients with metabolic syndrome by the assessment of brachial flow-mediated vasodilation (FMV) and intima-media thickening at both carotid and femoral sites. The purpose was to investigate the association of this metabolic disorder with prevalent atherosclerotic damage in different vascular sites. A control group of 87 healthy subjects was also investigated. Patients had lower values of FMV and a higher mean intima-media thickness (IMT) at both the carotid and femoral sites with respect to controls. Flow-mediated vasodilation had a positive correlation with high-density lipoprotein (HDL) cholesterol and a negative one with low-density lipoprotein (LDL) cholesterol, glycemia, and insulinemia. Carotid mean IMT was directly related to LDL cholesterol and age, and inversely with HDL cholesterol; femoral mean IMT had a direct association with LDL cholesterol, triglycerides, glycemia, and insulinemia and an inverse correlation with HDL cholesterol and LDL size. LDL cholesterol, HDL cholesterol, insulin, and brachial artery diameter were predictive of brachial FMV (beta=-0.17, 0.21, -0.27, and -0.29, respectively; P<.05), whereas age, LDL cholesterol, and HDL cholesterol were independent predictors of mean carotid IMT (beta=0.19, 0.37, and -0.27, respectively; P<.05); on the other hand, LDL cholesterol, triglycerides, and insulin were independent predictors of mean femoral IMT (beta=0.32, 0.26, and 0.25, respectively; P<.05). In conclusion, the present study documented an altered endothelial function and intima-media thickening in patients with metabolic syndrome without overt cardiovascular disease. Moreover, it focused on the strong influence of metabolic syndrome on preclinical atherosclerotic lesions at the femoral site.