Background Recently, vasodilators have been increasingly being recognized as useful for the treatment of acute heart failure syndromes (AHFS). Although carperitide (α-human atrial natriuretic peptide) has vasodilatory, diuretic and organ-protective effects, its efficacy and safety for the first-line drug treatment of AHFS have not been reported. Methods and Results A prospective observational study was performed in AHFS patients with preserved systolic blood pressure (SBP ≥120 mmHg), pulmonary congestion and dyspnea who were receiving carperitide monotherapy. The analysis was conducted in 1,832 patients (male: 52.7%; mean age: 75.1±12.7 years). The initial SBP was 151.1±25.7 mmHg; 62.0% were diagnosed as having acutely decompensated chronic heart failure and 78.8% were assessed as functional class III-IV according to New York Heart Association classification. Carperitide was administered at an initial dosage of 0.025-0.05 μg · kg^-1 · min^-1 in 50.4% of patients. In 1,524 patients (83.2%), carperitide monotherapy restored the acute phase and improved the degree of dyspnea as assessed using the modified Borg scale. The incidence of adverse drug reactions was 4.64%; the most frequently reported adverse reaction was hypotension (3.55%). Conclusion In the present study, following carperitide monotherapy, 83.2% of AHFS patients recovered from the acute phase. Based on these findings, carperitide seems useful for the first-line drug treatment of AHFS in patients with pulmonary congestion and preserved blood pressure. (Circ J 2008; 72: 1777 -1786)