Objectives: To evaluate the prevalence of cardiac injury and its association with mortality in hospitalized patients infected with avian influenza A (H7N9) virus. Design: Retrospective cohort study. Setting: A total of 133 hospitals in 17 provinces, autonomous regions, and municipalities of mainland China that admitted influenza A (H7N9) virus-infected patients between January 22, 2015, and June 16, 2017. Patients: A total of 321 patients with influenza A (H7N9) virus infection were included in the final analysis. Interventions: None. Measurements and Main Results: Demographics and clinical characteristics were collected from medical records. Cardiac injury was defined according to cardiac biomarkers, electrocardiography, or echocardiography. Among the 321 patients, 203 (63.2%) showed evidence of cardiac injury. Compared with the uninjured group, the cardiac injury group had lower Pao(2)/Fio(2) (median, 102.0 vs 148.4 mm Hg; p < 0.001), higher Acute Physiology and Chronic Health Evaluation II score (median, 17.0 vs 11.0; p < 0.001), longer stay in the ICU (10.0 vs 9.0 d; p = 0.029), and higher proportion of in-hospital death (64.0% vs 20.3%; p < 0.001). The proportion of virus clearance until discharge or death was lower in the cardiac injury group than in the uninjured group (58.6% vs 86.4%; p < 0.001). Multivariable-adjusted Cox proportional hazards regression analysis showed that cardiac injury was associated with higher mortality (hazards ratio, 2.06; 95% CI, 1.31-3.24) during hospitalization. Conclusions: Cardiac injury is a frequent condition among hospitalized patients infected with influenza A (H7N9) virus, and it is associated with higher risk of mortality.