Abstract: Objective: To investigate the effect of recombinant human brain natriuretic peptide on diuretics resistance in patients with heart failure.Methods: One hundred and twelve heart failure patients with diuretics resistance were selected and given routine drug treatment according to the guidelines. Furosemide 80 mg/d was given 48 hours before admission, but the 24-hour urine volume was less than 0.5 mL·kg^-1·h^-1. All patients were divided into the control group and treatment group, with 56 cases in each group. Patients in the control group were treated with furosemide 160 mg/d. In contrast, patients in the treatment group were treated with furosemide 80 mg/d and recombinant human brain natriuretic peptide continuously pumped for 72 hours after the loading dose. Effectiveness and safety indexes were observed. Effective indexes included daily urine volume, body weight change, and dyspnea score before and after three days. Safety indexes had systolic blood pressure, serum creatinine, blood Na⁺, and blood K⁺before and after treatment in the treatment group.Results: There was no statistical difference in gender, age, weight, course of the disease, left ventricular ejection fraction(LVEF), estimated glomerular filtration rate(eGFR), NYHA classification, and comorbidities between the two groups. The daily urine volume, weight loss, and increased value of dyspnea score in the treatment group were higher than those in the control group(all P<0.05). Eight cases(14.3%) in the treatment group had no significant urine volume changes, body weight and dyspnea scores before and after treatment. In comparison, 17 cases(30%) in the control group had poor curative effect. There was a significant difference in the proportion of patients with poor curative effect between the two groups(P<0.05). In the treatment group, there were no significant changes in systolic blood pressure, serum creatinine, and Na⁺before and after treatment(all P>0.05), but blood K⁺decreased(P<0.05).Conclusion: For patients with acute heart failure with reduced ejection fraction and diuretics resistance, recombinant human brain natriuretic peptide can increase the sensitivity of diuretics, relieve diuretics resistance, reduce weight, improve dyspnea, and the treatment process is safe.