Background:Postoperative radiotherapy (PORT) is commonly used to treat patients with resected stage III non-small cell lung cancer (NSCLC), but its effectiveness remains uncertain. This retrospective cohort study aimed to investigate the impact of PORT on overall survival (OS) and evaluate its heterogeneity among subgroups of patients.Methods:A total of 6305 patients with resected stage III NSCLC were included in this study from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching was conducted to balance baseline characteristics between the patients who received PORT and those who did not. OS was used as the primary outcome. Subgroup analysis was performed to identify which patient subgroups might benefit more from PORT.Results:Overall, no significant difference was observed in OS between the 2 groups with or without propensity score matching. However, subgroup analysis demonstrated that PORT improved OS in patients with certain characteristics, including stage IIIA/N2, stage IIIB, squamous cell carcinoma, tumor grade III-IV, or lymph node ratio (LNR) > 1/3. Multivariate analysis showed that several variables were associated with adverse prognostic factors for OS, such as marital status (others), race (white), male gender, squamous cell carcinoma, elderly age, advanced stage, poor histological differentiation grade, high LNR, and not receiving chemotherapy.Conclusion:In patients with resected stage III NSCLC, PORT may not be beneficial for all patients. However, it may improve survival time in certain patient subgroups, such as those with stage IIIA/N2, stage IIIB, squamous cell carcinoma, tumor grade III to IV, or LNR > 1/3. These findings provide important information for clinical decision-making and future research regarding the use of PORT in patients with resected stage III NSCLC.