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To elucidate the possible organ-protective effect of pharmacological postconditioning in patients undergoing liver resection with inflow occlusion.Inflow occlusion reduces blood loss during liver transection in selected patients but is potentially harmful due to ischemia-reperfusion injury. Preventive strategies include the use of repetitive short periods of ischemia interrupted by a reperfusion phase (intermittent clamping), application of a short period of ischemia before transection (ischemic preconditioning), or pharmacological preconditioning before transection. Whether intervention after resection (postconditioning) may confer protection is unknown.A 3 arm, prospective, randomized trial was designed for patients undergoing liver resection with inflow occlusion to compare the effects of pharmacological postconditioning with the volatile anesthetic agent sevoflurane (n = 48), intermittent clamping (n = 50), or no protective intervention (continuous inflow occlusion, n = 17). Endpoints included peak serum aspartate transaminase level, postoperative complications, and hospital stay. All patients were intravenously anesthetized with propofol. In patients with postconditioning, propofol infusion was stopped upon reperfusion and replaced with sevoflurane for 10 minutes.Compared with the control group, both postconditioning (P = 0.044) and intermittent clamping (P = 0.015) significantly reduced aspartate transaminase levels. The risk of complications was significantly decreased by postconditioning, odds ratio, 0.08 [95% confidence interval (CI), 0.02–0.36; P = 0.001]) and intermittent clamping, odds ratio, 0.50 [95% CI, 0.26–0.96; P = 0.038], compared with controls. Both interventions reduced length of hospital stay, postconditioning −4 days [95% CI, −6 to −1; P = 0.009], and intermittent clamping −2 days, [95% CI, −4 to 0; P = 0.019].Pharmacological postconditioning reduces organ injury and postoperative complications. This easily applicable strategy should be used in patients with prolonged continuous inflow occlusion.