Erlotinib is a potent reversible HER1/epidermal growth factor receptor tyrosine kinase inhibitor with single-agent activity in patients with non-small cell lung cancer. The aim of this study was to evaluate the efficacy of erlotinib for treating advanced non-small cell lung cancer by carrying out a pooled analysis of randomized controlled trials that compared erlotinib-based regimens with other agent-based regimens between January 1997 and 2011. Outcomes analyzed were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Fourteen trials including 7974 patients were identified. As first-line therapy was compared with chemotherapy, there was a similar ORR [OR: 0.33; 95% confidence interval (CI): 0.64-17.36; P=0.15], but decreased PFS [hazard ratio (HR): 1.55; 95% CI: 1.24-1.93; P<0.01] and OS (HR: 1.39; 95% CI: 0.99-1.94; P=0.05). As maintenance therapy was compared with placebo, erlotinib-based regimens significantly increased ORR (OR: 0.47; 95% CI: 0.31-0.70; P<0.01), prolonged PFS (HR: 0.71; 95% CI: 0.60-0.83; P<0.01), but did not improve OS (HR: 0.87; 95% CI: 0.68-1.11; P=0.22). As second/third-line therapy was compared with placebo, erlotinib-based regimens also significantly increased ORR (OR: 0.10; 95% CI: 0.02-0.41; P<0.01), prolonged PFS (HR: 0.61; 95% CI: 0.51-0.73; P<0.01), and improved OS (HR: 0.70; 95% CI: 0.58-0.84; P<0.01). However, as second/third-line therapy was compared with chemotherapy, the outcomes were similar between the two arms. When compared with PF299804, there was a decreased ORR (OR: 3.87; 95% CI: 1.27-11.81; P=0.02), and shortened PFS (HR: 0.58; 95% CI: 0.49-0.95; P=0.02). Meanwhile, erlotinib-based regimens showed no significant difference in adverse events, except for diarrhea, rash, and anemia. Erlotinib-based regimens significantly increased ORR and improved PFS as a first-line maintenance therapy or as a second/third-line therapy when compared with placebo.