Medium-chain (MCT) and long-chain (LCT) triglyceride diets were compared during and after 4 or 12 wk of hypocaloric feeding in obese women to determine the effects on weight loss, ketones, nitrogen balance, and insulin action. After a base-line euglycemic clamp, two groups ingested an 800-kcal/d liquid diet with 30% of calories as LCT (group 1) or 6% of calories as LCT and 24% as MCT (group 2). Rate and amount of weight loss, serum ketones, and N balance were not different between groups. However, the subjects in group 2 (MCT) demonstrated an increase in glucose requirement to maintain euglycemia during the clamp after weight loss (delta 0.18 +/- 0.13 mmol.m-2.min-1) whereas subjects in group 1 (LCT) had a diminished requirement (delta -0.12 +/- 0.10, p = 0.036). Thus, an 800-kcal diet containing 24% of calories as MCT is safe and enhances insulin action but fails to increase the rate or amount of weight loss.