The goal of this study was to compare the impact of differences in waist circumference (WC) defined according to the International Diabetes Federation (IDF) and the Adult Treatment Panel III (ATP III) and body mass index (BMI) on cardiovascular disease risk factors in 402 apparently healthy volunteers of European ancestry. Consequently, measurements were made of the WC, BMI, blood pressure, glucose, and lipid components of metabolic syndrome (MS) and insulin-mediated glucose uptake. Subjects were divided according to WC (IDF and ATP III criteria) and by normal weight, overweight, or obesity using BMI, and comparisons were made of the effect of these different indexes of adiposity on cardiovascular disease risk factors. The results indicated that WC and BMI significantly correlated (p <0.001) and were associated with differences in insulin-mediated glucose uptake to a similar degree in men (r = 0.57 and r = 0.59) and women (r = 0.53 and r = 0.52). Prevalences of MS were essentially identical irrespective of the measure of WC used (ATP III vs IDF), as were metabolic characteristics of those classified using IDF or ATP III criteria. Cardiovascular disease risk factor status did not vary substantially when subjects were divided on the basis of WC or BMI. In conclusion, prevalences of MS or cardiovascular disease risk factors did not vary as a function of differences in IDF and ATP III criteria for WC. BMI identified individuals at increased cardiovascular disease risk as effectively as determination of WC.