OBJECTIVE: The objective of this study was to determine associations of anthropometric measures of thigh and abdominal adipose tissue with metabolic risk factors, and whether these associations differed with ethnicity. We hypothesized that thigh circumference (ThC) would have an independent favorable association with insulin sensitivity, lipids, and blood pressure, whereas waist circumference (WC) would have an independent deleterious association with these variables in both African Americans (AA) and European Americans (EA). METHODS: Subjects were 228 healthy, overweight, premenopausal AA and EA women. Insulin sensitivity was assessed by intravenous glucose tolerance test and minimal modeling. Simple relationships between anthropometric measures and risk factors were determined by Pearson correlation analysis. Partial correlation coefficients were determined for circumference measures adjusted for thigh and abdominal skinfolds to differentiate relationships between thigh and abdominal subcutaneous fat from thigh muscle and deeper abdominal fat, respectively. RESULTS: In EA but not AA, ThC was positively associated with insulin sensitivity, independent of thigh skinfold. In both EA and AA, ThC was associated with a desirable lipid profile. In AA but not EA, WC was associated with lower insulin sensitivity and a less desirable metabolic profile. CONCLUSION: Results suggest that thigh muscle (ThC adjusted for thigh skinfold) may be metabolically protective in EA but not AA. In contrast, WC was a better indicator of insulin sensitivity and metabolic health in AA. Further investigation is needed to verify the association between thigh muscle and metabolic health, and to probe the reason for the observed ethnic specificity of the associations between anthropometric measures and metabolic risk factors.