Objective To study the efficacy of low-dose digoxin combined with hydrochlorothiazide and spironolactone in the treatment of elderly patients with heart failure and its influence on levels of cardiac troponin (cTnT), myocardial enzymology, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and inflammatory factors. Methods A total of 168 elderly patients with heart failure who were treated in the hospital were selected from June 2017 to July 2020 and were randomly divided into the observation group (low-dose digoxin combined with hydrochlorothiazide and spironolactone), the digoxin group (normal-dose digoxin combined with hydrochlorothiazide and spironolactone) and the control group (placebo combined with hydrochlorothiazide and spironolactone treatment), with 56 cases in each group. The efficacy of the three groups was compared, and the cardiac function ［left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF)］, myocardial enzymology ［creatine phosphokinase (CK), creatine phosphokinase isoenzyme (CK-MB), hydroxybutyrate dehydrogenase (HBDH)］, disease-related factors ［cTnT, NT-proBNP, interleukin-6 (IL-6)］ and quality of life ［Minnesota Living with Heart Failure Questionnaire (MLHFQ)］ were compared among the three groups before treatment and after 10 d of treatment. Results There was a statistically significant difference in the total effective rate among the three groups, and the total effective rate of observation group and digoxin group was significantly higher than that of the control group (P＜0.05). After 10 d of treatment, the levels of LVEDD and LVESD in the observation group and the digoxin group were significantly lower than those before treatment and those in the control group during the same period while the level of LVEF was significantly higher than that before treatment and that in the control group during the same period (P＜0.05). After 10 d of treatment, the levels of myocardial enzymology (CK, CK-MB, HBDH), disease-related factors (cTnT, NT-proBNP, IL-6) and MLHFQ in observation group and digoxin group were significantly lower than those before treatment and those in the control group during the same period (P＜0.05). There were no statistical differences in cardiac function (LVEDD, LVESD, LVEF), myocardial enzymology (CK, CK-MB, HBDH), disease-related factors (cTnT, NT-probNP, IL-6) and MLHFQ between the observation group and the digoxin group before and after treatment (P＞0.05). Conclusion Low-dose digoxin combined with hydrochlorothiazide and spironolactone in the treatment of elderly heart failure can improve the cardiac function and myocardial injury degree and enhance the quality of life, and has the same good efficacy as normal-dose digoxin.