Background <p>Oliceridine is a novel µ-opioid receptor agonist designed to reduce opioid-related adverse events while maintaining effective analgesia. However, randomized controlled trials comparing oliceridine with conventional opioids, such as sufentanil, have yielded inconsistent results. This systematic review and meta-analysis aims to compare the effects of oliceridine and sufentanil on postoperative nausea and vomiting.</p> Methods <p>We searched PubMed, Embase, and the Cochrane Library databases to identify all randomized controlled trials published from the inception through March 14, 2026, that examined the effects of oliceridine and sufentanil on postoperative nausea and vomiting. Data analysis was performed using RevMan 5.4 software. Binary outcomes were analyzed using risk ratios and 95% confidence intervals, while continuous variables were expressed as mean differences. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias Tool.</p> Results <p>Ten randomized controlled trials involving 1408 patients met the inclusion criteria. Compared with sufentanil, oliceridine was associated with a lower incidence of postoperative nausea and vomiting (RR = 0.46, 95% <i>CI</i> 0.36–0.58, <i>P</i> &lt; 0.00001), reduced requirement for rescue antiemetics (RR = 0.46, 95% <i>CI</i> 0.26–0.80, <i>P</i> = 0.006), and a lower incidence of respiratory depression (RR = 0.51, 95% <i>CI</i> 0.38–0.70, <i>P</i> &lt; 0.0001). No statistically significant differences were observed between groups in the number of effective activations of the analgesic pump, rescue analgesia, hypotension, bradycardia, and dizziness.</p> Conclusions <p>Oliceridine may reduce the risk of postoperative nausea and vomiting and respiratory depression compared with sufentanil while maintaining comparable analgesic efficacy. These findings support the potential role of oliceridine as an alternative opioid for perioperative analgesia.</p>