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. © 2010 Mosby, Inc. All rights reserved.