Background: Currently, targeted therapy has shown encouraging treatment benefits in selected patients with advanced non-small cell lung cancer (NSCLC). However, the comparative benefits of targeted drugs and chemotherapy (CT) treatments in unselected patients are not clear. We therefore conduct a network meta-analysis to assess the relative efficacy and safety of these regimens. Methods: PubMed, EMBASE, Cochrane Library and abstracts from major scientific meetings were searched for eligible literatures. The odds ratio (OR) for objective response rate (ORR) and safety was used for pooling effect sizes. Bayesian network meta-analysis was conducted to calculate the efficacy and safety of all included treatments. All tests of statistical significance were two sided. Results: A total of 13,060 patients from 24 randomized controlled trials (RCT) were assessed. The targeted agents included bevacizumab (Bev), gefitinib (Gef), erlotinib (Erl) and cetuximab (Cet). Network meta-analysis showed that Bev + CT had a statistically significantly higher incidence of ORR relative to the other six different treatments, including placebo (OR =6.47; 95% CI, 3.85-10.29), Erl (OR =2.81; 95% CI, 2.08-3.70), CT (OR =1.92; 95% CI, 1.61-2.28), Gef (OR =1.40; 95% CI, 1.10-1.75), Erl + CT (OR =1.46; 95% CI, 1.17-1.80) and Gef + CT (OR =1.75; 95% CI, 1.36-2.22), whereas placebo and Erl were associated with statistically significantly lower incidence of ORR. Trend analyses of rank probability revealed that Bev + CT had the highest probability of being the best treatment arm in term of ORR, followed by Cet + CT. Meanwhile, Cet + CT showed significant severer rash and thrombocytopenia compared with Bev + CT. Gef was probable to be the rank 3 for ORR but was associated with relatively low risk for grade >= 3 toxicities. Conclusions: Our study suggested that Bev + CT may offer better ORR in the treatment of unselected patients with advanced NSCLC. Future studies will be needed to investigate whether the increase of ORR with targeted drugs would be translated into survival benefits.