Objectives Effect of allopurinol on flow-mediated dilation (FMD), an index of endothelial function in humans, remains inconsistent.We performed a meta-analysis to determine whether allopurinol therapy could improve FMD.Methods and results Human intervention studies were identified by systematic searches of Medline, Embase, Cochranes library and references of related reviews and studies.A random-effect model was applied to estimate the pooled results.Meta-regression and subgroup analyses were performed to evaluate the impact of study characteristics on the effect of allopurinol on FMD.Ten randomized controlled trials with 594 subjects of cardiovascular risks were included.Results of the meta-analysis indicated that allopurinol therapy significantly improved FMD in these subjects as compare with control groups (WMD =1.67%, 95% CI: 0.83% ~ 2.50%, p < 0.001), although significant heterogeneity was detected (I2 =86%, p < 0.001).Results of meta-regression and subgroup analyses suggested that the benefit of allopurinol to FMD was independent of its uric acid (UA) lowering action.Moreover, allopurinol therapy may be associated with more remarkable improvement of FMD in subjects with lower serum UA (< 7 mg/dl: WMD =2.62%, 95% CI: 1.10% ~ 4.14%), compared to those with higher UA (≥ 7 mg/dl: WMD =0.87%, 95% CI: 0.37% ~ 1.38%; p for subgroup difference =0.03).Conclusions Allopurinol therapy is associated with significant improved endothelial function in subjects of CVD risks independent of its UA-lowering effect, and the beneficial effects of allopurinol seemed to be more remarkable in patients with normal UA at baseline.