Objective The standard first-line treatment for elderly patients with advanced NSCLC remains an open question.The aim of this study was to perform a systematic review and meta-analysis to support the choice of doublet or single cytotoxic agent therapy for the elderly with advanced non-small cell lung cancer in clinical setting.Methods: We searched PubMed, Embase, Cochrane databases and abstracts presented at ASCO, WCLC and ESMO for all eligible studies.The endpoints were overall survival, One-Year Survival Rate, Progression-Free Survival, overall response rate, and grade 3 or 4 adverse event.Subgroupanalysis was performed based on chemotherapy regimens, race and PS.We used Stata11.0 software and a fixed-effect or random-effect model in case of heterogeneity, and the results of the meta analysis were expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals (95%CI).Results: Of 215 potentially relevant publications, 13 randomized studies representing 3054 patients met inclusion criteria.The intention-to-treatment (ITT) analysis demonstrated that compared with single-agent chemotherapy, doublets induced a significantly increased OS (HR=0.83, 95% CI=0.71-0.97, p=0.019) and improvement in PFS (HR=0.78, 95% CI=0.62-1.00, p=0.047).The ORR was also significantly improved in the doublet group (RR=1.62 95% CI=1.41-1.87, p<0.001).Furthermore subgroup analysis indicated that the Asian population had less benefit from doublets compared with non-Asian population in terms of OS (HR=0.64, 95 % CI =0.33-1.23, p=0.181), One-Year Survival Rate (RR=1.09, 95% CI=0.79-1.52,p=0.602).Patients who were PS 0-2 seemed to have more benefit than PS 0-1 if doublet chemotherapy was administered in terms of OS (HR=0.84,95 % CI=0.72-0.98, p=0.026), Overall Response Rates (RR=1.61,95% CI=1.37-1.89, p<0.001).In addition, more incidences of grade 3 or 4 anemia, thrombocytopenia, fatigue were observed in the doublet combination group (anemia: RR=2.23, 95% CI=1.61-3.09, P<0.001; thrombocytopenia: RR=2.47, 95% CI=1.17-5.20, P=0.018; fatigue: RR=1.36, 95% CI=1.06-1.74, P=0.016).Conclusions: Doublets induced significantly increased OS and PFS compared with single agent.PS and race are both factors to choose doublet agent or single agent therapy as the first line treatment of NSCLC in the elderly.