Background and objective: Acute heart failure (AHF) is a complex clinical syndrome and frequently complicated by hypertension and atrial fibrillation (AF). The aim of this study was to evaluate whether urapidil provides additional therapeutic benefits compared to nitroglycerin (NG) in the treatment of AHF with hypertension and AF in elderly patients. Methods: 58 elderly patients from 10 hospitals were randomized into 2 groups. Control group (n=30) were treated with NG, while other group (n=28) were treated with urapidil. We monitored systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and carry out echocardiogram before and 24 h, 48 h, 72 h and 7 d after treatment with either NG or urapidil. Lipid profile, liver and kidney function, blood glucose levels in nitroglycerin and urapidil groups were examined before and 24 h, 48 h, and 7 d after treatment. Results: Patients receiving urapidil had lower SBP than that in NG group (P<0.05). Compared with NG group, patients in urapidil group showed increased LVEF (P<0.05), CO, SV and CI (P<0.05), but no significant differences in LVEDD and EDV. NT-proBNP was decreased following the treatment of urapidil or nitroglycerin, and the difference of NT-proBNP level was significant between the two groups (P<0.01) at 7 d. Urapidil had trend to decrease blood glucose after 7 d. Conclusions: Urapidil demonstrated better efficacy and fewer side effects than nitroglycerin on lowering and stabilizing systolic BP, attenuating cardiac afterload and improving cardiac function.