Seventy-two patients undergoing unilateral total hip replacement were randomized to receive either esketamine combined with dexmedetomidine (Es-D, n=38) or fentanyl combined with dexmedetomidine (F-D, n=34) via postoperative patient-controlled analgesia. The primary outcome of interest was postoperative analgesia, assessed by time to first rescue analgesia and total analgesic consumption. Secondary outcomes included visual analogue scale (VAS) scores for pain, sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI), and adverse events. Outcomes were assessed over a 48-hour postoperative period. Overall, the results of the study revealed that the Es-D group had longer time to first rescue analgesia, significantly lower cumulative analgesic use, and lower VAS scores during movement compared to the F-D group. However, sleep quality did not significantly differ between groups. These findings suggest that small-dose esketamine enhances analgesia while reducing opioid use and adverse effects, but does not improve sleep quality.