Background: We evaluated the incidence of postoperative acute kidney injury (AKI) and complications when remimazolam (RMMZ) or sevoflurane (SEVO) were used in elderly patients undergoing total knee arthroplasty. Methods: Seventy-eight participants aged ≥65 were randomly allocated to either the RMMZ or SEVO group. The primary outcome was the incidence of AKI on postoperative day (POD) 2. The secondary outcomes included intraoperative heart rate (HR), blood pressure (BP), total drug administered, emergence time, postoperative complications on POD 2, and hospital length of stay (HLOS). Results: The incidence of AKI was comparable between the RMMZ and SEVO groups. The doses of intraoperative remifentanil, vasodilators, and additional sedatives were significantly higher in the RMMZ group than in the SEVO group. Overall intraoperative HR and BP tended to remain higher in the RMMZ group. The emergence time in the operating room was significantly faster in the RMMZ group; however, the time required for an Aldrete score ≥ 9 was comparable between the RMMZ and SEVO groups. Postoperative complications and HLOS were comparable between the RMMZ and SEVO groups. Conclusion: RMMZ may be recommended for patients who are expected to decrease in intraoperative vital signs. However, stable hemodynamics with RMMZ were not sufficient to influence the prevention of AKI.