<p>Postoperative nausea and vomiting (PONV) are frequent complications that can occur after surgical procedures. Sugammadex, known for its effectiveness as a muscle relaxant antagonist, offers several advantages over neostigmine, however, there is still insufficient evidence to demonstrate its superiority in reducing PONV. This meta-analysis sought to assess the efficacy of sugammadex versus neostigmine in the management of PONV. Two independent investigators conducted a comprehensive review of randomized controlled trials (RCTs) across PubMed, Embase, and the Cochrane Library. The meta-analysis was performed using Review Manager software. Our meta-analysis scrutinized twenty studies that included 3248 participants. The results showed that sugammadex was effective in reducing postoperative nausea (RR = 0.65, 95% CI 0.48 to 0.88) versus neostigmine. Sugammadex reduced the dosage of opioids (SMD = 0.55, 95% CI −0.18 to 1.27) compared with neostigmine when the time of administration is T₂ (RR = 0.54, 95% CI 0.31 to 0.93). The use of sugammadex markedly lowered the occurrence of nausea during non-laparoscopic surgical procedures (RR = 0.42, 95% CI 0.27 to 0.65). This study demonstrated that sugammadex outperformed neostigmine in reducing PONV. Various factors, including the type of surgical procedure, timing of drug administration and dosage, might influence the efficacy of sugammadex.</p>