Background: Obesity is associated with numerous metabolic disturbances, such as insulin resistance, diabetes mellitus type 2, dyslipidemia, and hypertension. An excess of fat within the abdomen, so-called visceral adiposity, confers a greater and independent health risk of metabolic and cardiovascular complications than does adipose tissue accumulation elsewhere. The present study aimed to investigate a possible differential effect of diet-induced weight loss in visceral fat mass and metabolic parameters in obese individuals with the upper body (UBO) and lower body (LBO) obese phenotype. Methods: The obese subjects were prescribed a liquid, very-low calorie diet to reduce 50% of their overweight (15% body weight loss). Specific body fat measurements (MRI, BIA), anthropometrics, and fasting metabolic parameters were obtained in control subjects and two groups of obese subjects (UBO and LBO) before and after weight loss. Results: Weight loss was accompanied by significant decreases in total, subcutaneous, and visceral fat in both UBO and LBO women. The largest reduction in visceral fat mass was found in the UBO women (absolute decrease 223 ± 32 cm2 vs 122 ± 91 cm2 in LBO women; P = 0.01), while the amount of visceral fat was reduced to normal levels in LBO women (155 ± 25 cm2 after weight loss vs 143 ± 17 cm2 in controls; P = NS). Furthermore, weight loss significantly lowered fasting glucose, total cholesterol, and LDL cholesterol concentrations in UBO women. Conclusion: The obese phenotype is preserved after body weight loss. UBO women have to lose a larger amount of overweight in order to bring the amount of fat in the visceral depot down to normal levels and to obtain normalization of their cardiovascular risk profile.