Background & aims: Clinical outcome is negatively correlated to postoperative insulin resistance and hyperglycemia. The magnitude of insulin resistance can be modulated by glucose control, preoperative nutrition, adequate pain management and minimal invasive surgery. Effects of glucose control on perioperative glucose kinetics in liver surgery is less studied. Methods: 18 patients scheduled for open hepatectomy were studied per protocol in this prospective, randomized study. In the treatment group (n = 9), insulin was administered intravenously to keep arterial blood glucose between 6 and 8 mmol/l during surgery. The control group (n = 9) received insulin if blood glucose >11.5 mmol/l. Insulin sensitivity was measured by an insulin clamp on the day before surgery and immediately postoperatively. Glucose kinetics were assessed during the clamp and surgery. Results: Mean intraoperative glucose was 7.0 mM (SD 0.7) vs 9.1 mM (SD 1.9) in the insulin and control group respectively (p < 0.001; ANOVA). Insulin sensitivity decreased in both groups but significantly (p = 0.03, ANOVA) more in the control group (M value: 4.6 (4.4-6.8) to 2.1 (1.2-2.6) and 4.6 (4.1-5.0) to 0.6 (0.1-1.8) mg/kg/min in the treatment and control group respectively). Endogenous glucose production (EGP) increased and glucose disposal (WGD) decreased significantly between the pre-and postoperative clamps in both groups, with no significant difference between the groups. Intraoperative kinetics demonstrated that glucose control decreased EGP (p = 0.02) while WGD remained unchanged (p = 0.67). Conclusion: Glucose control reduces postoperative insulin resistance in liver surgery. EGP increases and WGD is diminished immediately postoperatively. Insulin seems to modulate both reactions, but mostly the WGD is affected. Intraoperative EGP decreased while WGD remained unaltered. Registration number of clinical trial: ANZCTR 12614000278639.