Objective To observe whether titration of recombinant human brain natriuretic peptide (rhBNP) is better than the current fixed-dose method and to evaluate its safety in the treatment of refractory acute decompensated heart failure. Methods Enrolled in the study were a total of 60 patients with acute and chronic decompensated heart failure with left ventricular ejection fraction lower than 35% in NYHA cardiac function grades IVa and IVb. They were randomly divided into two groups:fixed-dose group and titrated-dose group, with 30 in each group. The fixed-dose group was not given a preload, and the rhBNP 0.015μg/(kgmin) was intravenously pumped for 48 hours according to the baseline blood pressure. The titrated-dose group was first loaded with rhBNP 1.5μg/kg and titrated with an initial dose of 0.0075μg/(kgmin), which was increased by 0.0025μg every 15min until the maximum of 0.030μg/(kgmin); or the dose was titratably increased based on the target blood pressure and maintained for 48-96h after the target blood pressure was achieved. Indicators observed included improvement of subjective symptoms, 24-hour cumulative urine volume, systolic blood pressure and mean arterial pressure, heart rate and heart rhythm, aldosterone, serum creatinine and creatinine clearance before and after drug administration. SPSS statistics 18.0 was used for data analysis. The measurement data were expressed as mean±standard deviation (±s), and the t test was used for comparison between groups; the numeration data were expressed as the number of cases (percentage), and the χ² test was used for comparison between groups. Results Compared with the fixed-dose group, the titrated-dose group had more obvious relief of heart failure symptoms, better improvement rate and higher urine volume at the initial 24 hours, greater decrease of NT-proBNP, greater increase in pulmonary artery pressure, and more improved ventricular artery coupling ratio, the differences being statistically significant (P<0.05). Conclusion Titrated dose of rhBNP can relieve the clinical symptoms of acute heart failure faster than the fixed dose, with the safety being not inferior to that of the latter. The efficacy and tolerability are better in the patients with normal or high baseline blood pressure and severe systemic congestion.