Introduction <p>Postoperative delirium (POD) is a common postoperative complication and is associated with numerous adverse outcomes. Advanced age and hip surgery are high risk factors for POD. Both remimazolam tosilate for injection and sevoflurane can be used as sedatives for the maintenance of general anesthesia, but the comparison of their impacts on the incidence of POD has not been reported. This study aims to compare the effect of remimazolam tosilate vernus sevoflurane on the incidence of POD in older patients undergoing total hip arthroplasty.</p> Methods and analysis <p>This is a two-arm, parallel, prospective, multicenter, randomized controlled trial. A total of 456 older patients at six clinical trial centers in China will be randomly assigned in a 1:1 ratio to receive general anesthesia with remimazolam tosilate or sevoflurane as sedative. The primary outcome measure is the prevalence of POD during the first 4 postoperative days. Secondary outcomes include cognitive function [Mini-Mental State Examination (MMSE)], perioperative pain degree [Visual Analogue Scale (VAS)], postoperative nausea and vomiting (PONV) within 4 days after surgery, recovery time after drug withdrawal, the amount of vasoactive drugs used during operation, length of hospital stay, and in-hospital complications.</p> Ethics and dissemination <p>The Research Ethics Committee of Qilu Hospital of Shandong University has approved the study protocol (REF: KYLL-202206-25), which is applicable to all research centers. Participant recruitment begins in August 2022. Written informed consent will be obtained from each patient before randomization. The findings will be published in an international peer-reviewed medical journal.</p> Trial registration <p>The trial has been registered at the Chinese Clinical Trial Registry: ChiCTR2200062455; date of registration: 2022-08-08.</p>