Abstract: Background　Elderly patients with advanced non-small cell lung cancer (NSCLC) face challenges in treatment due to increased comorbidities, organ function decline and immunosenescence. Although immune checkpoint inhibitors have shown therapeutic potential, their efficacy and safety in patients aged ≥75 years still need further validation through real-world studies. Objective　To evaluate the efficacy, safety, and associated factors of immunotherapy in patients aged 75 years and older with advanced NSCLC. Methods　A retrospective analysis was conducted on patients aged ≥75 years with advanced NSCLC who received immunotherapy in Chinese PLA General Hospital from January 2016 to October 2024. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Cox proportional hazards regression models were used to identify factors associated with OS and PFS, and result robustness was assessed using Bootstrap resampling. Inverse probability of treatment weighting (IPTW) was applied to compare immunotherapy monotherapy with immunotherapy combined with chemotherapy. A 3-month landmark analysis was performed to evaluate the association between early immune-related adverse events (irAE) and survival outcomes. Results　A total of 102 patients with advanced NSCLC aged ≥75 years were included, with a median age of 78.0(IQR: 76.0 - 80.0) years. Among them, 81 patients (79.4%) were male. The median follow-up time was 21.1(IQR: 10.7 - 37.2) months. The median OS was 27.9(95% CI: 21.0 - 34.9) months, and the median PFS was 11.1(95%CI: 8.3 - 20.1) months. The ORR and DCR were 42.2% and 93.1%, respectively. After IPTW adjustment, no statistically significant differences in OS or PFS were observed between immunotherapy plus chemotherapy and immunotherapy monotherapy(P＞0.05). AEs of any grade occurred in 86.3% of patients, and grade ≥3 AEs occurred in 22.6%. The overall incidence of irAE was 40.2%, predominantly grade 1 - 2, with a median onset time of 3.0(IQR: 1.2 - 7.4) months. The 3-month landmark analysis showed no significant association between early irAE and OS or PFS (P＞0.05). Conclusion　Immunotherapy is generally effective and tolerable in patients aged ≥75 years with advanced NSCLC and can provide durable survival benefits. However, patients aged ≥80 years and those with poor ECOG performance status have significantly worse prognosis. Immunotherapy combined with chemotherapy does not demonstrate a clear survival advantage over immunotherapy monotherapy. Individualized immunotherapy strategies should be developed based on comprehensive assessment of functional status and treatment tolerance.