OBJECTIVES: Evidence remains conflicting about whether exogenous testosterone increases cardiovascular events. We systematically evaluated evidence of the direction and magnitude of association between exogenous testosterone and cardiovascular events; exploring discordance between existing systematic review findings. METHODS: Two independent reviewers screened 950 full texts of 21,903 initial abstracts, and identified all published systematic reviews or meta-analyses evaluating cardiovascular effects of exogenous testosterone on males aged 18 years or older from January 1966 through November 2015. We extracted data on study characteristics; analytic methods; key findings; and applied a checklist for assessing the methodological quality of systematic reviews (AMSTAR). RESULTS: We identified seven systematic reviews that included six meta-analyses. The number of included trials ranged from 3 to 75 and study participants ranged from 308 to 5464. Four meta-analyses reported no significant association between exogenous testosterone and cardiovascular events (odds ratio [OR] 1.14, 95% confidence intervals [CI] 0.59-2.20 by Calof et al; OR 1.82, CI 0.78-4.23 by Haddad et al; relative risk [RR] 1.12, CI 0.70- 1.81 by Fernandez-Balsells et al; Mantel-Haenszel OR 1.07, CI 0.69-1.65 by Corona et al. A qualitative review by Carson et al also reported that testosterone does not increase cardiovascular risk. Conversely, two meta-analyses reported a significant association between testosterone and cardiovascular risk (OR 1.54, CI 1.09-2.18 by Xu et al; and RR 2.20, CI 1.45-3.55 by Borst et al). Four reviews examined disaggregated cardiovascular outcomes while three examined composite events. We observed significant clinical heterogeneity, differing statistical methods, and variable methodological quality. AMSTAR scores ranged from 1 to 9 out of 11. CONCLUSIONS: Different outcomes, analytic methods and study quality may explain the discordant systematic reviews. Given the challenge of adequately powering clinical trials for these rare outcomes, rigorous observational studies examining major cardiovascular outcomes are needed to help clarify this association.