AIM: To investigate the effect of sakubatril valsartan combined with dagliflozin in the treatment of patients with HFrEF and the effect on serum cardiac troponin I (CTnI) and B-type brain natriuretic peptide (BNP) levels.  METHODS: Seventy patients with HFrEF admitted to our hospital from January 2020 to October 2021 were selected and divided, using random number table method, into control group (35 cases, conventional treatment + sakubatril valsartan) and observation group (35 cases, conventional treatment + sakubatril valsartan + dagliflozin). The treatment effect, myocardial markers (serum cTnI, BNP), exercise capacity ( 6 min walking experiment), myocardial remodeling-related indexes ［(left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic internal diameter (LVESD), left ventricular ejection fraction (LVEF)］ and adverse effects were compared between the two groups. RESULTS: The total effective rate of treatment in the observation group was lower than that in the control group (P<0.05), and the difference was not statistically significant (P>0.05); the changing trends of serum BNP and cTnI expressions were the same in the two groups at 3 months and 6 months of treatment, and the serum BNP and cTnI expressions of patients in the observation group were lower than those in the control group (P<0.05); at the end of treatment, the 6 min walk test results of patients in the observation group were better than those in the control group (P<0.05); At the end of treatment, the LVEDd and LVESD values in the observation group were lower than those in the control group, and the LVEF values were higher than those in the control group (P<0.05); the differences were not statistically significant when comparing the total incidence of adverse reactions between the two groups (P>0.05). CONCLUSION: The combination of sakubatril valsartan and dagliflozin is effective for patients with HFrEF, and can effectively regulate serum cTnI and BNP levels with low adverse reactions.