Femoral-gluteal adipose tissue (AT) may be cardioprotective through fatty acids uptake. Femoral-gluteal AT has previously been defined as leg fat measured by dual energy X-ray absorptiometry (DXA), however, subcutaneous adipose tissue (SAT) and intermuscular adipose tissue (IMAT) are inseparable using DXA. This study investigated the independent relationships between femoral-gluteal SAT, femoral-gluteal IMAT and cardiovascular disease (CVD) risk factors (fasting serum measures of glucose, total cholesterol (TC), high density lipoprotein cholesterol (HDLC), triglycerides (TG) and insulin) and whether race differences exist in femoral-gluteal AT distribution. Adult Caucasians (56 men and 104 women), African-Americans (37 men and 76 women), and Asians (11 men and 35 women) had total AT (TAT) including femoral-gluteal AT (upper leg SAT and IMAT) and visceral AT (VAT) by magnetic resonance imaging (MRI). General linear models identified the independent effects of femoral-gluteal SAT and femoral-gluteal IMAT on each risk factor after covarying for TAT, VAT, age, race, sex and 2-way interactions. Femoral-gluteal IMAT and glucose (p<0.05) were positively associated independent of VAT. There were also significant inverse associations between femoral-gluteal SAT and insulin (p<0.01) and TG (p<0.05) although the addition of VAT rendered these effects non-significant, possibly due to collinearity. Asian women had less femoral-gluteal SAT and greater VAT than Caucasians and African-Americans (p<0.05) and Asian and African-American men had greater femoral-gluteal IMAT than Caucasians, adjusted for age and TAT (p<0.05 for both). Femoral-gluteal SAT and femoral-gluteal IMAT distribution varies by sex and race and these two components have independent and opposing relationships with CVD risk factors.