We examined the effects of a 10–14-weeks inpatient lifestyle modification program, including minimum 90 min of physical activity (PA) five days/week, on body composition, CVD risk factors, and eating behavior in 139 obese subjects (BMI 42.6±5.2 kg/m2). Completion rate was 71% (n=71) in the intensive lifestyle intervention (ILI) group and 85% (n=33) among waiting list controls. Compared to controls body weight (-17.0 (95% CI: -18.7, -15.3) kg, P<0.0001), fat mass (-15.2 (95% CI: -17.4, -13.1) kg, P<0.0001), fat free mass (-1.2 (95% CI: -2.2, -0.2) kg, P=0.016) and visceral fat (-86.6(95% CI: -97.4, -75.7) cm2, P<0.0001) were reduced in the ILI-group after 10–14 weeks. Within the ILI-group weight loss was -23.8 (95% CI: -25.9, -21.7) kg, P<0.0001 and -20.3 (95% CI: -23.3, -17.3) kg, P<0.0001, after six and 12 months, respectively. Systolic BP, glucose, triglycerides, and LDL-C were reduced, and HDL-C was increased (all P≤0.006) after 10–14 weeks within the ILI group. The reduction in glucose and increase in HDL-C were sustained after 12 months (all P<0.0001). After one year, weight loss was related to increased cognitive restraint and decreased uncontrolled eating (all P<0.05). Thus, ILI including high volume of PA resulted in weight loss with almost maintenance of fat-free mass, favorable changes in CVD risk factors, and eating behavior in subjects with severe obesity.