Abstract: Objective To explore the effect of bisoprolol combined with enalapril and spironolactone on cardiac function and prognosis of patients with heart failure induced by rheumatic heart disease. Methods A total of 210 patients with heart failure induced by rheumatic heart disease were randomly divided into single group and combined group, with 105 cases in each group. Single group was treated with enalapril and spironolactone, and combined group was additional treated with bisoprolol on the basis of the single group. The cardiac function grading of New York Heart Association(NYHA), cardiac function indexes, levels of plasma brain natriuretic peptide(BNP)and N-terminal pro-brain natriuretic peptide(NT-proBNP), 6 min walking distance, cumulative survival rate and the incidence of adverse reactions were compared between the two groups. Results After treatment, the cardiac function grading of NYHA in combined group was significantly better than that in single group(P<0.05). The left ventricular end diastolic diameter(LVEDD)and left ventricular end systolic diameter(LVESD)in both groups were significantly lower than those before treatment(P<0.05), while the left ventricular ejection fraction(LVEF)was significantly higher than that before treatment - (P<0.05), and the changes in combined group were significantly greater than those in single group (P<0.05). The levels of BNP and NT-proBNP in both groups were significantly lower than those before treatment(P<0.05), and the reductions in combined group were significantly greater than those in single group(P<0.05). The 6 min walking distance in both groups was significantly increased when compared with that before treatment(P<0.05), and the combined group was significantly better than that in single group(P<0.05). The survival rates at 3, 6 and 12 months after hospital discharge in combined group were significantly higher than those in single group(P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05). Conclusion Bisoprolol combined with enalapril and spironolactone is effective and safe in the treatment of patients with heart failure induced by rheumatic heart disease, which can significantly improve cardiac function status, reduce levels of BNP and NT-proBNP, increase 6 min walking distance, and improve cumulative survival rate.