The aim of the study was to determine what effect weight loss had on intra-abdominal adipose tissue (IAAT) and cardiovascular disease (CVD) risk in 135 premenopausal overweight African-American (AA) and European-American (EA) women matched for BMI. Blood lipids, systolic blood pressure (SBP), diastolic BP (DBP), and IAAT (computed tomography determined) were examined prior to and after an 800 kcal/day diet producing 12 kg-weight loss. Significant decreases in IAAT (∼38%), total cholesterol (TC; 3%), low-density lipoproteins (LDLs: 6%), triglycerides (TGs: 27%), cholesterol/high-density lipoprotein ratio (C/HDL ratio: 18%), SBP (3%), and DBP (3%) occurred while HDL increased (16%), following weight loss and 1 month energy balance. Significant interactions between time and race showed that AA women decreased TG and increased HDL proportionately less than EA women. After adjusting for ΔIAAT, none of the CVD variables significantly changed after weight loss with the exception of HDL and C/HDL ratio. After adjusting for ΔLF (leg fat), ΔTC, ΔTG, ΔLDL, and ΔC/HDL ratio were significantly different. Multiple regression showed that independent of each other, ΔIAAT was significantly and positively related to ΔTC (adjusted Β = 0.24) and ΔTG (adjusted Β = 0.47), and ΔLF was negatively related to ΔTC (adjusted Β = 0.19) and ΔTG (adjusted Β = 0.18). Overweight and premenopausal AA and EA women benefitted from weight loss by decreasing IAAT and improving CVD risk. The changes in IAAT were significantly related to blood lipids, but loss of LF seems to be related to reduced improvement in TC and TG. Based on these results, interventions should focus on changes on IAAT. © 2009 The Obesity Society.