AIM: This study aims to investigate whether pupillary light reflex (PLR) parameters in dynamic pupillometry can effectively predict postoperative nausea and vomiting (PONV). METHODS: In this prospective observational study, patients scheduled to undergo elective lobectomy under general anesthesia were enrolled from 1 August 2023 to 7 October 2023 at Yantai Yuhuangding Hospital, a large regional tertiary hospital in Yantai City, Shandong Province, China. Preoperative pupillary parameters were measured using a portable infrared pupillometer, and the patients were followed up within 24 hours postoperatively to assess postoperative nausea and vomiting (PONV) and recovery quality. Logistic regression analysis and receiver operating characteristics (ROC) curves were used to evaluate the predictive efficacy of pupillary parameters, and mediation analysis was conducted to explore the mediating role of PONV between pupillary parameters and recovery quality. RESULTS: Forty-six patients (29.9%) who experienced PONV had smaller maximum pupil diameter, average constriction velocity (ACV), maximum constriction velocity (MCV), and percentage pupil change. MCV was identified as an independent predictor of PONV, with each 1-unit increase in MCV reducing the risk of PONV by 87%. Gender was a protective factor, with males having a 65% lower risk of PONV compared to females. The ROC analysis showed that the area under the curve (AUC) value of MCV was 0.831 (95% confidence interval (CI): 0.760–0.902), indicating that the model has strong classification ability when using MCV as a predictor. Thus, PONV plays a full mediating role in the relationship between MCV and postoperative recovery quality. CONCLUSIONS: MCV is a reliable predictor of PONV, which plays a full mediating role in the relationship between MCV and postoperative recovery quality. Thus, with a capability in predicting PONV occurrence, preoperative MCV measurement can be employed for the purpose of improving patient recovery outcomes. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300073869).