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β-Blocker exposure has been shown to reduce mortality in traumatic brain injury (TBI); however, the efficacy of β-blockers remains inconclusive. Therefore, a meta-analysis was conducted in this paper to evaluate the safety and efficacy of β-blocker therapy on patients with TBI.The electronic databases were systemically retrieved from construction to February 2017. The odds ratio (OR), mean difference (MD) and 95% confidence intervals (CI) were determined.A total of 13 observational cohort studies involving 15,734 cases were enrolled. The results indicated that β-blocker therapy had remarkably reduced the in-hospital mortality (OR 0.33; 95% CI 0.27–0.40; p < 0.001). However, β-blocker therapy was also associated with increased infection rate (OR 2.01; 95% CI 1.50–2.69; p < 0.001), longer length of stay (MD = 7.40; 95% CI = 4.39, 10.41; p < 0.001) and ICU stay (MD = 3.52; 95% CI = 1.56, 5.47; p < 0.001). In addition, β-blocker therapy also led to longer period of ventilator support (MD = 2.70; 95% CI = 1.81, 3.59; p < 0.001).The meta-analysis demonstrates that β-blockers are effective in lowering mortality in patients with TBI. However, β-blocker therapy has markedly increased the infection rate and requires a longer period of ventilator support, intensive care management as well as length of stay.β-Blockers were effective in lowering mortality in patients with TBI.β-Blocker therapy significantly increases the risk of infection rates.β-Blocker therapy required a longer period of ventilator support and intensive care management.Suggestions for future research are given.