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Influenza infection is associated with increased risk for mortality and hospitalization in heart failure patients. Although there are no published randomized controlled trials examining the effect of influenza vaccination on clinical outcomes in heart failure patients, the effect has been examined in observational cohort studies. Nevertheless, results are inconsistent due partly to limited power with small sample sizes and use of different definitions of outcomes. We therefore aimed to conduct a systematic review and meta-analysis of the effect of influenza vaccination on mortality and hospitalization in heart failure patients. The search of electronic databases identified 6 observational cohort studies with 22,486 patients examining the effect of influenza vaccination on mortality and hospitalization in heart failure patients. Pooled analysis of confounder-adjusted hazard ratio showed that influenza vaccination was associated with reduced risk of mortality during 1-year follow-up (risk ratio [95% CI] = 0.76 [0.63–0.92],
P
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< 0.01) and during long-term (up to 4 years) follow-up (0.80 [0.71–0.90],
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< 0.001). Furthermore, influenza vaccination was associated with reduced risk of mortality during influenza season (risk ratio [95% CI] = 0.52 [0.39–0.69],
P
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< 0.001) and during non-influenza season (0.79 [0.69–0.90],
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< 0.001). Only a few studies reported the effect of influenza vaccination on hospitalization, which did not permit us to perform pooled analysis. In conclusion, our meta-analysis showed that influenza vaccination was associated with reduced risk of mortality in heart failure patients. Large-scale and adequately powered randomized controlled trials should be planned to confirm our observed potential survival benefit of influenza vaccination in these patients.