The metabolic syndrome (MS), a clustering of metabolic disturbances, is associated with increased cardiovascular risk. Limited information is available about the relations between MS, insulin resistance, and vascular function. We measured brachial artery flow-mediated dilation (n = 2,123) and reactive hyperemia (n = 1,521) in Framingham Offspring participants without diabetes or clinical cardiovascular disease (mean age 59 +/- 9 years, 57% women). MS, determined by National Cholesterol Education Program criteria, was present in 36% of participants. Insulin resistance was determined using Homeostatic Model Assessment. In age- and gender-adjusted models, MS was associated with lower flow-mediated dilation and reactive hyperemia. There was progressively lower vasodilator function with increasing number of MS components (p for trend <0.0001). In multivariable models adjusting for the 5 MS components as continuous variables, MS (presence vs absence) remained associated with lower flow-mediated dilation (2.84 +/- 0.12% vs 3.17 +/- 0.08%, p = 0.0496) and reactive hyperemia (50.8 +/- 1.0 vs 54.4 +/- 0.7 cm/s, p = 0.009). Insulin resistance was inversely associated with flow-mediated dilation and reactive hyperemia in age- and gender-adjusted models, but these relations were not significant in models adjusting for the MS components. In conclusion, our observations are consistent with the hypothesis that MS and insulin resistance impair vascular function predominantly through the influence of the component metabolic abnormalities that comprise MS.