Purpose: To compare survivals between unresectable stage III and stage IV EGFR-mutated non-small cell lung cancer (NSCLC) patients receiving first-line EGFR-TKI.Materials and methods: Unresectable stage III and stage IV EGFR-mutated NSCLC patients were investigated from September 2012 to May 2022. Patients received EGFR-TKI as the first-line treatment. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method and propensity score matching (PSM) analyses.Results: A total of 558 patients were included: 478 (85.66%) patients were stage IV and 80 (14.34%) patients were stage III. Before PSM, stage III patients showed a better median PFS (15 vs. 13 months;P=0.026) and a similar median OS (29 vs. 30 months;P=0.820) compared to stage IV patients. Stage IV was an independent prognostic factor for PFS [hazard ratio (HR)=1.47, 95% confidence interval (CI): 1.06-2.04;P=0.021], but not for OS (HR=1.11, 95% CI: 0.77-1.60;P=0.560). After PSM, a better median PFS (15 vs. 12 months;P=0.016) and a similar median OS (29 vs. 30 months;P=0.960) were found between stage III and stage IV patients.Conclusions: OS was similar between unresectable stage III and stage IV EGFR-mutated NSCLC patients receiving EGFR-TKI as the first-line treatment.