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 (approximately 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 Delta IAAT, none of the CVD variables significantly changed after weight loss with the exception of HDL and C/HDL ratio. After adjusting for Delta LF (leg fat), Delta TC, Delta TG, Delta LDL, and Delta C/HDL ratio were significantly different. Multiple regression showed that independent of each other, Delta IAAT was significantly and positively related to Delta TC (adjusted beta = 0.24) and Delta TG (adjusted beta = 0.47), and Delta LF was negatively related to Delta TC (adjusted beta = -0.19) and Delta TG (adjusted beta = -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.