Abstract: To explore the effect of high-fat diet on delayed pleural effusion after single-port video-assisted thoracoscopic lung surgery.. Methods:?A retrospective analysis was conducted on the clinical data of 571 patients who underwent single-port video-assisted thoracoscopic lung surgery at the Department of Thoracic Surgery, Nanjing Medical University Affiliated Brain Hospital from December 2021 to June 2023. Patients were divided into high-fat diet group and non-high-fat diet according to a high-fat diet was adopted postoperatively. Propensity score matching analysis was used to match the two groups of patients with a ratio of 1:1, and then the incidence of delayed pleural effusion and other postoperative complications was compared between the matched groups. Results: Before matching, the high-fat diet group included 166 patients, with 45 males and 121 females, and a median age of 56.0 (49.0–66.0) years. The control group included 405 patients, with 164 males and 241 females, and a median age of 57.0 (48.0–67.0) years. After propensity score matching, each group included 130 patients. The high-fat diet group showed significantly higher incidences of delayed pleural effusion (OR=1.080, 95% CI=1.013–1.152, P=0.019), postoperative cough (OR=1.203, 95% CI=1.091–1.326, P=0.001), and postoperative chest tightness (OR=1.166, 95% CI=1.038–1.311, P=0.010) compared to the non-high-fat diet group, with statistically significant differences. Conclusion: A high-fat diet after single-port thoracoscopic lung surgery can significantly increase the incidence of delayed pleural effusion.