BACKGROUND AND AIMS: Remote ischemic conditioning (RIC) has shown promise in preclinical and clinical studies, but its effectiveness in reducing hepatic ischemia-reperfusion injuries (HIRIs) and enhancing postoperative recovery after hepatectomy remains uncertain. In this study, we aimed to evaluate the impact of perioperative RIC (PRIC) on postoperative recovery in patients undergoing hepatectomy. METHODS: A randomised controlled trial was performed. A total of 135 eligible patients were randomised to either a control group (sham RIC), a PRIC-1 group (RIC once daily for 3 days starting on the day of surgery) or a PRIC-2 group (RIC twice daily). The primary outcome was the time to 2 times the upper limit of normal (2ULN) alanine transaminase (ALT) levels post-hepatectomy. Secondary outcomes included time to reach 2ULN for aspartate transaminase (AST) levels, the area under the concentration-time curve on postoperative Day 7 (AUC-POD7) for ALT, AST, total bilirubin and lactic acid, as well as assessments of gastrointestinal function and postoperative complications. RESULTS: Median time to 2ULN ALT was shorter in the PRIC-1 and PRIC-2 groups than in the control group (PRIC-1: 5.0 [3.5, 6.0] vs. control: 7.0 [7.0, 10.0] days, p <
0.001
PRIC-2: 5.0 [4.0, 8.0] vs. control: 7.0 [7.0, 10.0] days, p <
0.001). The AUC-POD7 for ALT and AST, time to 2ULN AST, time to gastrointestinal tolerance and postoperative complications were significantly improved in the PRIC groups compared with thecontrols. CONCLUSIONS: PRIC is safe and effective in reducing HIRIs and enhancing recovery post-hepatectomy. Once-daily PRIC offers similar benefits to twice-daily PRIC. TRIAL REGISTRATION: NCT06130436 (ClinicalTrials.gov).