Background The International Diabetes Federation (IDF) and Adult Treatment Panel (ATP) III define metabolic syndrome (MetSyn) differently, with unclear implications for cardiovascular disease (CVD) risk. Methods We examined 22,719 participants in the REGARDS study. We classified participants as: no MetSyn, MetSyn by ATP-III and IDF criteria, MetSyn by ATP-only, or MetSyn by IDF-only. To assess current CVD, we determined the odds of self-reported CVD by MetSyn category using multivariable logistic regression, controlling for socio-demographic and behavioral factors. To estimate future coronary heart disease risk, we calculated Framingham risk scores (FRS). Results Overall, 10,785 individuals (47%) had MetSyn. Of these, 79% had MetSyn by both definitions, 6% by ATP-only, and 14% by IDF-only. Compared to those without MetSyn, ATP-only individuals had the highest odds of current CVD and of having a FRS >20%. Also compared to those without MetSyn, IDF-only individuals had 43% higher odds of current CVD and 2-fold increased odds of having a FRS >20%. Conclusions Consistent with previous reports, ATP-III MetSyn criteria identified individuals with increased odds of CVD and elevated future coronary heart disease risk. However, the IDF definition identified a clinically important number of additional individuals at excess CVD risk. (Am Heart J 2010; 159: 385-91.)