Purpose <p>Oliceridine is a G protein-biased μ-opioid receptor agonist that selectively activates G protein signaling while significantly reducing β-arrestin pathway recruitment. Clinical data indicate that this unique signaling bias may help mitigate common adverse effects associated with traditional opioids. The objective of this study was to compare the effects of oliceridine and sufentanil on postoperative recovery quality in patients undergoing hysteroscopic surgery.</p> Methods <p>In this prospective, double-blind, randomized controlled trial, 108 patients undergoing hysteroscopic surgery were enrolled and randomly assigned to either the oliceridine group (Group O) or the sufentanil group (Group S). The primary outcome was the 15-item Quality of Recovery Scale (QoR-15) score assessed at 24&#xa0;h post-operatively.</p> Results <p>One hundred one patients were included in the analysis (Group O: <i>n</i> = 51; Group S: <i>n</i> = 50). At 24&#xa0;h post-operatively, Group O had significantly higher total QoR-15 scores than Group S did (123 [IQR 120–125] vs. 116.5 [IQR 114–118]; difference = 6.5, <i>P</i> &lt; 0.001). Group O also scored higher on specific QoR-15 domains: enjoyment of food, general well-being, and nausea or vomiting. Adverse events were less common in Group O, which had significantly lower rates of respiratory depression and nausea/vomiting. Intraoperative monitoring revealed less pronounced effects on heart and respiratory rates in Group O vs. Group S. No statistically significant differences were observed in sedation onset time, total propofol dose, or emergence time.</p> Conclusion <p>When compared with sufentanil, oliceridine significantly enhanced early postoperative recovery quality in patients undergoing hysteroscopic surgery while reducing the incidence of respiratory depression and nausea/vomiting.</p>