BACKGROUND: Acute kidney injury is a common complication after open total aortic arch replacement but lacks effective preventive strategies. Remote ischemic preconditioning has controversial results of its benefit to the kidney and may perform better in high-risk patients of acute kidney injury. We investigated whether remote ischemic preconditioning would prevent postoperative acute kidney injury after open total aortic arch replacement. METHODS: We enrolled 130 patients scheduled for open total aortic arch replacement and randomized them to receive either remote ischemic preconditioning (4 cycles of 5-minute right upper limb ischemia and 5-minute reperfusion) or sham preconditioning (4 cycles of 5-minute right upper limb pseudo ischemia and 5-minute reperfusion), both via blood pressure cuff inflation and deflation. The primary end point was the incidence of acute kidney injury within 7 days after the surgery defined by the Kidney Disease: Improving Global Outcomes criteria. Secondary end point included short-term clinical outcomes. RESULTS: Significantly fewer patients developed postoperative acute kidney injury with remote ischemic preconditioning compared with sham (55.4% vs 73.8%; absolute risk reduction, 18.5%; 95% CI, 2.3%-34.6%; P = .028). Remote ischemic preconditioning significantly reduced acute kidney injury stage II-III (10.8% vs 35.4%; P = .001). Remote ischemic preconditioning shortened the mechanical ventilation duration (18 hours [interquartile range, 14-33] versus 25 hours [interquartile range, 17-48]; P = .01), whereas no significant differences were observed between groups in other secondary outcomes. CONCLUSIONS: Remote ischemic preconditioning prevented acute kidney injury after open total aortic arch replacement, especially severe acute kidney injury and shortened mechanical ventilation duration. The observed renoprotective effects of remote ischemic preconditioning require further investigation in both clinical research and the underlying mechanism.