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INTRODUCTION To determine whether an upfront combination compared to single-agent therapy is beneficial for elderly patients with advanced non-small cell lung cancer (NSCLC) in the real world, a population-based epidemiologic study was conducted. METHODS Patients ≥70 years with advanced NSCLC from 2007 to 2012 were identified in the National Health Insurance Service Database of Korea. A Cox proportional-hazards regression model and propensity score analysis were used to examine the effect of treatment modality on survival. RESULTS Among 41,276 patients newly diagnosed with lung cancer, 8274 (20.0%) identified to be treated with upfront palliative chemotherapy were eligible for this study. After excluding 976 patients who received a first-line anti-epidermal growth factor receptor (EGFR) treatment, 7298 (88.2%) who received cytotoxic chemotherapy were included in further analyses: 5636 (77.2%) received doublet chemotherapy and 1662 (22.8%) received monotherapy. The most frequent regimen in combination group was gemcitabine and platinum doublet (44.7%), whereas that in monotherapy group was gemcitabine (46.7%). Multivariate analyses indicated lower use of combination chemotherapy with increasing age (odds ratio [OR] 0.73; 95% CI 0.67-0.79; P < 0.001) and female sex (OR 0.71; 95% CI 0.62-0.80; P < 0.001). Receipt of combination over single-agent chemotherapy was associated with a reduced risk of death (hazard ratio [HR] 0.91; 95% CI 0.86-0.96; P = 0.001) in overall population and (HR 0.89; 95% CI 0.80-0.98; P = 0.019) in the propensity-matched cohort. CONCLUSION In elderly patients with advanced NSCLC excluding those receiving frontline anti-EGFR targeted agents, receiving initial combination chemotherapy compared to single-agent was associated with improved survival.