This study was designed to investigate the effect of low dose nesiritide on renal function and major cardiac events in patients with acute decompensated heart failure (ADHF) following acute myocardial infarction (AMI). Sixty patients were randomized into nesiritide (loading dose 0.5'g/kg'maintenance dose 0.0075'g/kg/min) and nitroprusside group. Compared with nitroprusside group, nesiritide group had a greater heart rate reduction (P<0.05), higher 24h urine volume (P<0.001) and more significant alleviation in dyspnea (P<0.001). The prevalence of hypotension in the nesiritide group was lower than in the nitroprusside group (7.4%) vs 28.5%, P<0.05). Nesiritide group had a greater reduction in serum noradrenaline, angiotensin II, aldosterone, endothelin and NT-proBNP (all P<0.01). The mean serum creatinine in the nesiritide group was reduced (109.4±26.6 vs 102.8±21.6 'mol/L, P<0.01), whereas it remained unchanged in the nitroprusside group (106.8±20 vs 106.0±19.2 'mol/L, P>0.05). The rehospitalization or mortality rate was similar between the two groups three months after the therapy (P>0.05). We conclude that low dose nesiritide is more effective in suppressing the activation of the sympathetic and rennin-angiotensin systems. It also improves the clinical symptoms and enhances renal function, but its effect on hospital readmission or mortality rate needs further investigation.