Objective To investigate the efficacy and safety of Oselidine in patient-controlled intravenous analgesia （PCIA） for elderly patients after total knee arthroplasty （TKA）. Methods A prospective， double-blind， single-center， randomized controlled study design was employed. A total of 84 patients who were undergoing elective TKA under general anesthesia were recruited and randomly allocated to either the oseltidine group or the sufentanil group， with 42 cases in each group. All patients received PCIA 48 hours after the operation. The primary endpoint was the static visual analogue scale （VAS） score 24 hours after the operation， while the secondary endpoints were the static and dynamic VAS scores at 6， 12， 24， and 48 hours after the operation. The time of the first PCIA pressing after operation， the effective number of PCIA pressings within 48 h after operation （D1）， the total number of PCIA pressings within 48 h after operation （D2）， the ratio of D1 to D2， and the incidence of remedial analgesia. The Ramsay sedation scores at 5， 10， 20， and 30 min after extubation， the Quality of Recovery-15 （QoR-15） scores at 24 h before operation， 24 h， and 48 h after operation， the Athens Insomnia Scale （AIS） scores on the night before operation， the first night， and the second night after operation， the satisfaction score， and the postoperative hospital stay. Adverse events （such as nausea and vomiting， respiratory depression， urinary retention， dizziness， etc.） that occurred within 48 h after surgery. Results There were no significant differences in VAS score， Ramsay score， analgesia pump pressing - related indexes， and the incidence of remedial analgesia between the two groups at all time points （P > 0.05）. The D1/D2 ratio， QoR-15 scores at 24 and 48 h after operation， and the satisfaction score in the oseltidine group were higher than those in the sufentanil group （P < 0.05）. The AIS score on the first night after operation and the incidence of nausea and vomiting in the oseltidine group were lower than those in the sufentanil group （P < 0.05）. Conclusions This study systematically compared the analgesic efficacy and safety of oxycodone and sufentanil as PCIA drugs in patients with TKA. Results indicate that oxycodone not only provides analgesia comparable to sufentanil but also demonstrates significant advantages in terms of safety and patient comfort. Oxycodone significantly reduced the incidence of postoperative nausea and vomiting， while enhancing the quality of postoperative recovery， sleep quality， and overall patient satisfaction.