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Background The effect of statins on plasma concentrations of vascular endothelial growth factor (VEGF), the main angiogenic growth factor with pro-inflammatory and atherogenic properties, is controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to obtain a conclusive result in humans. Methods PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched to identify RCTs investigating the impact of statins on plasma VEGF concentrations. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Meta-regression, sensitivity analysis and publication bias assessments were performed using standard methods. Results Eight RCTs examining the effects of statins on plasma VEGF concentrations were included. Meta-analysis suggested a significant reduction of plasma VEGF levels following statin therapy (weighed mean difference: − 19.88 pg/mL, 95% CI: − 35.87, − 3.89, p = 0.015). VEGF reductions were observed in the subsets of trials with treatment durations ≥ 4 weeks (− 19.54, − 37.78, − 1.30, p = 0.036), LDL-C reductions ≥ 50 mg/dL (− 28.59, − 43.68, − 13.50, p p = 0.017), and diseased populations (− 21.08, − 39.97, − 2.18, p = 0.029), but not in the opposite subsets. Meta-regression also suggested a significant association between changes in plasma VEGF levels and LDL-C changes, treatment duration, but not molar dose of statins. Conclusions These results suggest a significant reduction in plasma VEGF concentrations following statin therapy. This effect depends on duration of treatment, LDL-lowering activity, lipophilicity of statins, and health status of studied individuals. Further RCTs are needed to explore if the VEGF reduction is implicated in the statin benefits on cardiovascular outcomes.