Abstract：Objective：To observe the clinical effect of Shenmai Injection combined with Metoprolol for heart failure. Methods：A total of 80 cases of patients with heart failure were selected as the study objects and divided into two groups according to the random number table method，with 40 cases in each group. The study group was treated with Shenmai Injection combined with Metoprolol，and the control group was simply treated with Metoprolol. Both groups were treated for 14 days. After treatment，the clinical effects were compared between the two groups. Before and after treatment，and the heart function indexes and the expression levels of high mobility group protein B1 (HMGB1)， receptor for advanced glycation end products (RAGE) and N- terminal pro- brain natriuretic peptide (NT- proBNP) in serum were compared between the two groups. After 12- month outpatient and telephone follow- up ， the incidence of cardiovascular events was compared between the two groups. Results： The total effective rate was 95.00% in the study group，higher than that of 72.50% in the control group (P＜0.05). Before treatment， there was no significant difference being found in the comparison of left ventricular end-diastolic diameter (LVEDD) ， left ventricular end- systolic diameter(LVESD) ， and left ventricular ejection fraction(LVEF) between the two groups (P＞0.05). After treatment，LVEDD and LVESD in the two groups were decreased (P＜0.05)， and LVEF was increased (P＜0.05)； LVEDD and LVESD in the study group were lower than those in the control group (P＜0.05)，and LVEF was higher than that in the control group (P＜0.05). Before treatment， there was no significant difference being found in the comparison of the levels of HMGB1， RAGE， and NT- proBNP in serum between the two groups (P＞0.05). After treatment， the levels of HMGB1，RAGE，and NT- proBNP in serum in the two groups were decreased (P＜0.05)，and the above levels in the study group were lower than those in the control group (P＜0.05). The total incidence of cardiovascular events was 7.50% in the study group，lower than that of 25.00% in the control group (P＜ 0.05). Conclusion：Shenmai Injection combined with Metoprolol for patients with heart failure can enhance the clinical effect，improve heart function indexes，and reduce the incidence of cardiovascular events.