Purpose <p>Intraoperative nausea and vomiting are common during cesarean delivery under neuraxial anesthesia, and peritoneal traction is a major trigger. Flurbiprofen, a non-steroidal anti-inflammatory drug used for multimodal analgesia, is typically administered toward the end of surgery; whether earlier intraoperative administration is associated with reduced intraoperative nausea and vomiting remains unclear.</p> Methods <p>We conducted a retrospective cohort study at a single tertiary university hospital in Japan from October 1, 2021 to September 30, 2025. Parturients undergoing cesarean delivery under neuraxial anesthesia were classified as an early group (intravenous flurbiprofen administered after umbilical cord clamping and by the start of peritoneal closure) or a non-early group (administered after the start of peritoneal closure or not administered intraoperatively). The primary outcome was intraoperative antiemetic use, pre-specified as a surrogate for intraoperative nausea and vomiting. Adjusted odds ratios were estimated using multivariable logistic regression with pre-specified sensitivity analyses.</p> Results <p>A total of 1398 parturients were included (early, <i>n</i> = 1062; non-early, <i>n</i> = 336). Intraoperative antiemetic use occurred in 172/1,062 (16.2%) and 91/336 (27.1%), respectively, corresponding to an absolute risk difference of − 10.9 percentage points. Early flurbiprofen administration was associated with lower odds of intraoperative antiemetic use (adjusted odds ratio 0.54; 95% confidence interval 0.41 to 0.73; <i>P</i> &lt; 0.001), with consistent findings across sensitivity analyses.</p> Conclusion <p>Early intraoperative flurbiprofen administration after umbilical cord clamping was associated with lower intraoperative antiemetic use during cesarean delivery under neuraxial anesthesia, suggesting that the timing of routine non-steroidal anti-inflammatory drug administration may be relevant to intraoperative nausea and vomiting management.</p>