The metabolic syndrome may be a common phenotype increasing risk for type 2 diabetes and cardiovascular disease. We assessed the prevalence and characteristics of the metabolic syndrome among population-based samples of 3,224 white subjects attending Framingham Offspring Study (FOS) exam 5 (1991–1995) and 1,081 non-Hispanic white and 1,656 Mexican-American subjects attending the San Antonio Heart Study (SAHS) phase II follow-up exam (1992–1996). Subjects were ∼50% women, aged 30–79 years, without diabetes, and classified with the metabolic syndrome according to criteria for obesity, dyslipidemia, hyperglycemia, and hypertension proposed by the Third Report of the National Cholesterol Education Program’s Adult Treatment Panel (ATP III) or the World Health Organization (WHO). We used regression models to estimate rates across ethnic groups and to assess the association of the metabolic syndrome with insulin resistance and predicted 10-year coronary heart disease (CHD) risk. Among FOS white subjects, the age- and sex-adjusted prevalence of the metabolic syndrome was 24% by both ATP III and WHO criteria; among SAHS non-Hispanic white subjects, 23 and 21%, respectively; and among SAHS Mexican-American subjects, 31 and 30%. Rates were highest among Mexican-American women (ATP III, 33%) and lowest among white women (21%). Subjects with the metabolic syndrome by ATP III criteria had higher age-, sex-, and ethnicity-adjusted levels of fasting insulin (11.3 μU/ml), homeostasis model assessment of insulin resistance (2.7), and predicted CHD risk (11.8%) than those without the syndrome (5.9 μU/ml, 1.3, and 6.4%, respectively; all P = 0.0001); differences were similar using WHO criteria. We conclude that the metabolic syndrome typically affects 20–30% of middle-aged adults in the U.S. By any criteria, subjects with the metabolic syndrome are more insulin resistant and at increased predicted risk for CHD versus those without the metabolic syndrome.