OBJECTIVE: To assess the efficacy of targeted agents (TAs) in the treatment of elderly patients with advanced gastric cancer (AGC). MATERIALS AND METHODS: Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to December 31, 2015 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials (RCTs) evaluating therapies with or without TAs in elderly patients with AGC. The endpoints were overall survival (OS) and progression-free survival (PFS). Statistical analyses were conducted by using Comprehensive Meta Analysis software (Version 2.0). RESULTS: A total of 1,759 elderly patients with AGC from ten RCTs were included for analysis. The pooled results demonstrated that the addition of TAs to therapies in elderly patients significantly improved OS (HR 0.88, 95% CI: 0.79-0.99, p = 0.032), but not for PFS (HR 0.83, 95% CI: 0.66-1.06, p = 0.13) when compared to controls. Subgroup analysis according to targeted agents indicated that survival benefit was observed for antiHER- 2 agents (HR 0.71, 95% CI: 0.55-0.91, p = 0.006) and angiogenesis inhibitors (AIs) (HR 0.78, 95% CI: 0.62-0.99, p = 0.04) in terms of OS. Conversely, no survival benefit was found for anti-EGFR agents in terms of OS (HR 1.12, 95% CI: 0.93-1.36, p = 0.24) and PFS (HR 1.35, 95% CI: 0.88-2.07, p = 0.17). No publication bias was detected by Begg's and Egger's tests for OS. CONCLUSIONS: The findings of this study suggest that the addition of TAs to therapies in elderly patients with AGC offers an improved OS, which can be ascribed to AIs and ant-HER2 agents. With available evidence, anti-EGFR agents could not be recommended for use in elderly AGC patients.