Cardiac surgery triggers an inflammatory stress response leading to protein catabolism, a process which even high-dose insulin therapy alone cannot reverse. To determine whether hyperinsulinemic-normoglycemic clamp and perioperative amino acid supplementation improves whole-body protein balance, twenty patients scheduled for elective coronary artery bypass grafting surgery were randomly assigned to have intra and postoperative hyperinsulinemic-normoglycemic clamp with or without intravenous amino acid (AA) supplementation. Primed continuous infusions of [6,6-²H₂]glucose and L-[1-¹³C]leucine were used to quantify whole-body protein and glucose metabolism before and after surgery. Adipose tissue and serum cytokines were also analyzed to measure their responsiveness to the anabolic effect of amino acid administration. During hyperinsulinemic-normoglycemic clamp, amino acid supplementation successfully stimulated whole-body protein synthesis, resulting in a positive whole-body protein balance after surgery (insulin: -13.6 +/- 4.5 vs insulin+AA: 2.1 +/- 5.4 micromol/kg/h, P<0.001). Endogenous glucose production was equally suppressed in both groups (insulin: 0.0 +/- 3.8 vs insulin+AA 1.6 +/- 1.6 micromol/kg/min, P=0.230). Amino acid supplementation led to significant changes in serum and tissue IL-6 (insulin: 246.6 +/- 111.2 vs insulin+AA: 124.5 +/- 79.3 pg/mL, P=0.011). In conclusion, hyperinsulinemic-normoglycemic clamp technique together with AA supplementation can induce an anabolic state after open-heart surgery as quantified by a positive whole body protein balance.