AimIt is not clear whether treatment by vascular endothelial growth factor (VEGF) gene transfer can improve myocardial ischemia through a proangiogenesis mechanism and is effective against coronary artery disease (CAD). We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared VEGF gene therapy and standard treatments in CAD. MethodsWe systematically searched the PubMed, Embase, and Cochrane databases and relevant references for RCTs (published up to May 2018; no language restrictions) and performed meta-analysis using both fixed and random effects models. Our primary outcome measures were mortality and serious cardiac events. The secondary outcome measures were follow-up left ventricular ejection fraction (LVEF), change in LVEF (LVEF), and angina outcomes. The registration number is CRD42017058430. ResultsOf 524 identified studies, 14 were eligible and were included in our analysis. At a mean follow-up of 6months, VEGF gene therapy demonstrated a decreased risk of serious cardiac events (11.7% vs 21.2%, relative risk: 0.56; 95% confidence interval (CI): 0.37, 0.84; P=0.005) and a slight improvement in follow-up LVEF (weighted mean difference: 1.95; 95%CI: 1.28, 2.62). Furthermore, VEGF gene therapy using adenoviral vectors showed more potential benefit in terms of the risk of serious cardiac events, LVEF, and Canadian Cardiovascular Society angina class. Nevertheless, mortality and angina frequency scores were not different. ConclusionsVascular endothelial growth factor gene therapy appears to be safe and effective regarding serious cardiac events, with greater benefit when using adenoviral vectors. This meta-analysis highlights the need for further exploration in these areas.