One hundred twenty elderly patients (aged 60–90 years) undergoing knee arthroplasty under general anesthesia were randomized to receive either ephedrine (n=60) or phenylephrine (n=60) to maintain intraoperative blood pressure. The primary outcome was the incidence of postoperative delirium (POD) within three days post-surgery. Secondary outcomes included changes in cardiac output (CO), regional cerebral oxygen saturation (rSO2), mean arterial pressure (MAP), heart rate (HR), postoperative complications, and hospital stay. Outcomes were assessed daily for three days postoperatively. Overall, the results indicated that the incidence of POD on the first postoperative day was significantly lower in the ephedrine group compared to the phenylephrine group. The ephedrine group also exhibited higher CO and rSO2 levels during surgery. However, no significant differences in POD were observed on the second and third postoperative days. These findings suggest that ephedrine may be superior to phenylephrine in reducing early POD, likely due to better cerebral perfusion and oxygenation.