Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been approved by the U.S. Food and Drug Administration in treating T790M mutationpositive advanced non-small cell lung cancer (NSCLC). A systematic review and meta-analysis was conducted to assess the efficacy and safety of osimertinib in treating advanced NSCLC patients with acquired T790M mutation. PubMed, EMBASE, Cochrane Library and Web of Science were searched to obtain the eligible studies following the "population, interventions, comparisons, outcomes, study design" (PICOS) criteria. The pooled analysis of objective response rate (ORR), disease controlled rate (DCR), progressionfree survival (PFS), overall survival (OS) and adverse events (AEs) were performed using STATA12.0 and RevMan5.0. A total of 1,050 patients were included in the meta-analysis. The combined osimertinib ORR was 0.64 (95% CI, 0.60-0.69), the ORR of central nervous system (CNS) was 0.54 (95% CI, 0.37-0.71), DCR was 0.89 (95% CI, 0.86-0.92), PFS at six months (PFS-6m) rate was 0.69 (95% CI, 0.58-0.79), PFS at one year (PFS-1y) rate was 0.33 (95% CI, 0.20-0.46), OS at one year (OS-1y) rate was 0.69 (95% CI, 0.55-0.84). The pooled incidence rate of the AEs of grade ≥ III was 0.25 (95% CI, 0.09-0.40). The results from Begg's and Egger's tests presented no publication bias in the included studies. Osimertinib demonstrated a superior therapeutic benefit with high efficacy and low toxicity for T790M-positive advanced NSCLC patients who were treated with early-generation EGFR-TKIs. Meanwhile, osimertinib showed promising for the treatment of advanced patients with CNS metastases.