The explanation for the rapid improvement in insulin resistance after Roux-en Y gastric bypass (RYGB) may involve mechanisms additional to caloric restriction and improvements in peripheral glucose disposal. 8 severely obese patients underwent a 6-day very low calorie diet (VLCD) (456 kcal/day) followed 1-3 weeks later by RYGB. Insulin resistance was measured by short intravenous insulin tolerance test (IVITT) and by homeostasis model assessment (HOMA) before and again 6 days after the VLCD and after RYGB. In a group of 24 matched patients, HOMA assessments were made before and six days after RYGB. HOMA-IR fell significantly from 6.84.9 to 4.32.9 (p < 0.05) following VLCD, but this was less than the subsequent fall following RYGB (6.8 ± 4.9 to 1.50.4, p < 0.01). Control patients who underwent RYGB alone, reduced their HOMA-IR to 1.50.9 following the operation which was not significantly different from the VLCD then RYGB group. Following VLCD, IVITT showed no significant change. However, 6 days after RYGB, IVITT showed worsened insulin induced glucose uptake (p < 0.05). Patients undergoing VLCD over six days had a reduction in HOMA-IR which was half that of patients undergoing RYGB. Patients who underwent both VLCD and RYGB had a total reduction in HOMA similar to those who underwent the RYGB alone. In contrast, IVITT showed a worsening in insulin induced glucose disposal following RYGB, which suggests worsening peripheral insulin resistance. This study supports the hypothesis that mechanisms other than caloric restriction are involved in the acute improvement in HOMA-IR following RYGB.