We tested the hypothesis that perioperative amino acid supplementation of hypocaloric dextrose would attenuate the inhibitory effect of glucose on endogenous glucose production after surgery. Sixteen patients undergoing colorectal cancer surgery were randomly assigned to receive intravenous glucose either with or without amino acids. Nutrition was administered over 48 hours from surgical skin incision until the second postoperative day. Glucose provided 50% and amino acids 20% of the patient's measured resting energy expenditure. Glucose rate of appearance was assessed by [6,6-2H2]glucose before and after surgery. Circulating concentrations of glucose, lactate, insulin, and glucagon were also determined. Hypocaloric glucose suppressed postoperative endogenous glucose production to a similar degree in both groups. The circulating concentrations of glucose increased to the same extent, whereas there was no significant change in plasma concentrations of lactate, glucagon, and cortisol. Postoperative plasma levels of insulin were significantly higher in patients receiving amino acids (P = .009). Perioperative amino acid administration does not mitigate the inhibitory effect of glucose on glucose production or aggravate hyperglycemia after colorectal surgery.