Background: Whether preoperative exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with postoperative nausea and vomiting (PONY) after laparoscopic sleeve gastrectomy (LSG) remains unclear. Objectives: To investigate the association between preoperative GLP-1RAs exposure and PONY after LSG. Setting: University Hospital, China. Methods: We reviewed a retrospective cohort of patients underwent LSG between January 1, 2017, and December 30, 2021 at Nanjing Drum Tower Hospital, dividing the patients into 2 groups on the basis of whether they were exposed to GLP-1RAs preoperatively. A 1:1 propensity score matching was performed to balance the characteristics between the groups. Associations between GLP1RAs exposure and PONY were determined by logistic regressions. Results: A total of 564 eligible patients underwent LSG, 351 (62.2%, 95% CI 58.2-66.1) of whom had PONY. In total cohort, PONY occurred in 72(84.7%) patients exposed to GLP-1RAs preoperatively and 279 (58.2%) patients not exposed to GLP-1RAs (adjusted odds ratio 6.782, 95% confidence interval 3.307-13.907, P < .001). In the 158 matched patients, PONY occurred in 66 (83.5%) patients exposed to GLP-1RAs preoperatively and 48 (60.8%) matched patients not exposed to GLP-1RAs (adjusted odds ratio 3.830, 95% confidence interval 1.461-10.036, P 5 .006). Subgroup analysis by dosage forms and doses revealed a positive association between greater doses and an increased risk of PONY after LSG for both once-daily and once-weekly formulations. Conclusions: Preoperative exposure to GLP-1RAs is associated with an increased risk of PONY in patients undergoing LSG, particularly at higher doses of exposure. (Surg Obes Relat Dis 2025;21:247-255.) (c) 2025 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.