In the present study, we evaluated the efficacy and safety of epidermal growth factor receptor tyrosine kinases (EGFR-TKIs) combined with or without angiogenesis inhibitors in advanced non-small-cell lung cancer (NSCLC). We searched published randomized controlled trials (RCTs) comparing EGFR-TKIs with and without angiogenesis inhibitors for the treatment of advanced NSCLC. PubMed, EMBASE, PMC, the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) databases were searched. The extracted data on progression-free survival (PFS) and overall survival (OS) were measured in terms of hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). In addition, odds ratios (ORs) and corresponding 95% CIs were pooled for objective response rate (ORR) and disease control rate (DCR). Risk ratios (RRs) and corresponding 95% CIs were pooled for risk of adverse events (AEs). EGFR-TKIs combined with angiogenesis inhibitors showed significant improvements in PFS (HR 0.72, 95% CI 0.61-0.84, P <0.0001), ORR (OR 1.51, 95% CI 1.17-1.97, P=0.002) and DCR (OR 1.49, 95% CI 1.24-1.81, P<0.0001) compared with EGFR-TKIs combined with placebo. However, EGFR-TKIs combined with angiogenesis inhibitors failed to improve OS (HR 0.94, 95% CI 0.84-1.05, P = 0.26). In addition, diarrhea, hypertension, thrombocytopenia, neutropenia, fatigue, rash, and dermatitis acneiform were significantly increased in patients treated with angiogenesis inhibitors. Thus, EGFR-TKIs combined with angiogenesis inhibitors were superior to EGFR-TKIs alone in advanced NSCLC due to their effects on PFS, ORR and DCR, but the increased incidence of AEs had an influence on the tolerability of this combination therapy.