Current targets for body mass index (BMI) and waist circumference (WC) may not be appropriate for those of South Asian origin. The objectives of this study were to determine whether the relationship between BMI and WC with risk factors for cardiovascular disease (CVD) is the same for men and women of South Asian and European descent. Apparently healthy men and women of European (n = 88) and South Asian (n = 93) descent were recruited from 3 hospital communities and assessed for BMI, WC, waist-to-hip ratio (WHR), blood pressure (BP), lipids, insulin, glucose, and CRP. The study cohort was stratified by sex, and regression analyses were performed with individual risk factors as outcomes and ethnicity with either BMI or WC as predictors adjusting for age and height (WC only). BMI and WC were similar between the European and South Asian men and women. South Asian men had significantly higher values for total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), total cholesterol:high-density lipoprotein-cholesterol (HDL-C) and CRP, and significantly lower values of HDL-C. South Asian women had significantly higher values for TG, TC:HDL-C and CRP and significantly lower values of HDL-C, glucose, systolic BP and diastolic BP. In men, ethnicity was an independent predictor for all risk factors except for glucose and insulin, after adjusting for either BMI or WC independent of age and height. For women, ethnicity was an independent predictor for all risk factors except for total cholesterol (WC model only) and insulin (BMI model only), after adjusting for either BMI or WC independent of age and height. The relationship between BMI or WC and risk factors is such that men and women of South Asian descent present with a more adverse risk profile than those of European descent at the same BMI and/or WC.