Objective To investigate the therapeutic efficacy of Shenmai injection combined with milrinone in acute heart failure and its influence on inflammatory factors, myocardial enzymes and brain natriuretic peptide (BNP).Methods The 96 patients with acute heart failure in our hospital from January 2018 to September 2020 were randomly divided into treatment group (48 cases) and control group (48 cases). The control group was treated with milrinone, and the treatment group was treated with Shenmai Injection on the basis of the control group. The treatment course of the two groups was 7 days. The overall effective rate after treatment, and the changes of cardiac function [left ventricular end-diastolic dimension (LVDd) and left ventricular ejection fraction (LVEF)], inflammatory factors [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)], myocardial enzymes [creatine kinase (CK), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB) and cardiac troponin I (cTnI)] and BNP levels before and after 7 days of treatment were compared.Results The overall effective rate (91.67%) was higher in the treatment group than that in the control group (72.92%) (P < 0.05). The differences of LVDd and LVEF before and after treatment in the treatment group were higher than those in the control group (P < 0.05). Besides, the difference in levels of TNF-α, IL-6, CK, LDH, CK-MB, cTnI and BNP before and after the treatment in the treatment group were higher than those in the control group (P < 0.05).Conclusions Shenmai injection combined with milrinone has a good curative effect on patients with acute heart failure. It can ameliorate inflammatory reaction, improve myocardial enzyme spectrum and reduce BNP level.