To compare the effects of equivalent weight loss induced by two bariatric surgical techniques on insulin action in severely obese patients. Eighteen nondiabetic patients with severe obesity (mean [± SD] body mass index: 53.5 ± 9.0 kg/m 2) and 20 sex- and age-matched lean subjects (body mass index: 23.8 ± 3.0 kg/m 2) underwent metabolic studies, including measurement of insulin sensitivity by the insulin clamp technique. Patients then underwent either vertical banded gastroplasty with Roux-en-Y gastric bypass, or biliopancreatic diversion, and were restudied at 5 to 6 months and again at 16 to 24 months postsurgery. At baseline, patients were hyperinsulinemic (194 ± 47 pmol/L vs. 55 ± 25 pmol/L, P < 0.0001), hypertriglyceridemic (1.56 ± 0.30 mmol/L vs. 0.78 ± 0.32 mmol/L, P < 0.0001), and profoundly insulin resistant (insulin-mediated glucose disposal: 20.8 ± 4.4 μmol/min/kg fat-free mass vs. 52.0 ± 10.1 μmol/min/kg, P < 0.0001) as compared with controls. Weight loss by the two procedures was equivalent in both amount (averaging -53 kg) and time course. In the gastric bypass group, insulin sensitivity improved (23.8 ± 6.0 μmol/min/kg at 5 months and 33.7 ± 11.3 μmol/min/kg at 16 months, P < 0.01 vs. baseline and controls). In contrast, in the biliopancreatic diversion group, insulin sensitivity was normalized already at 6 months (52.5 ± 12.4 μmol/min/kg, P = 0.72 vs. controls) and increased further at 24 months (68.7 ± 9.5 μmol/min/kg, P < 0.01 vs. controls) despite a persistent obese phenotype (body mass index: 33.2 ± 8.0 kg/m 2). In surgically treated obese patients, insulin sensitivity improves in proportion to weight loss with use of predominantly restrictive procedures (gastric bypass), but is reversed completely by predominantly malabsorptive approaches (biliopancreatic diversion) long before normalization of body weight. Selective nutrient absorption and gut hormones may interact with one another in the genesis of the metabolic abnormalities of obesity.