Objective: To explore the effect of enalapril combined with hydrochlorothiazide and indapamide on hypertension and heart failure. Methods: 80 patients with hypertension and heart failure admitted to our hospital from January 2019 to January 2020 were selected as the research subjects, and they were divided into two groups with random number table method, 40 cases each. The control group was given conventional treatment regimens, including enalapril and hydrochlorothiazide; the observation group replaced hydrochlorothiazide with indapamide based on the above therapies. The efficacy and systolic blood pressure, diastolic blood pressure and left heart ejection fraction (LVEF) of the two groups were compared. Results: After treatment, the effective rate of the observation group was 92.50% (37/40) higher than that of the control group 75.00% (30/40). The systolic and diastolic blood pressure were lower than those of the control group, and the LVEF was higher than that of the control group. The difference was statistically significant (P<0.05). Conclusion: Enalapril combined with indapamide is effective in the treatment of hypertension with heart failure, which can help lower blood pressure, reduce heart load, increase cardiac output, reverse ventricular remodeling, and delay disease progression.