The Prospective Randomized Outcomes study of Acutely decompensated Congestive heart failure Treated Initially as Outpatients with Nesiritide (PROACTION) trial evaluated the safety of nesiritide administration in the emergency department in patients with decompensated heart failure. Patients (N=237) were treated for at least 12 hours with standard care plus either intravenous nesiritide or placebo. Compared to placebo, nesiritide favorably decreased systolic blood pressure (SBP) in patients with elevated baseline SBP, without negatively impacting patients with lower baseline SBP (SBP, >140 mm Hg: nesiritide, -28.7 mm Hg, vs placebo, -8.4 mm Hg [P<.001]; SBP, 101-140 mm Hg: nesiritide, -12.3 mm Hg, vs placebo, -5 mm Hg [P<.017]; SBP, <101 mm Hg: nesiritide, -1.2 mm Hg vs placebo, +16.7 mm Hg [P<.03]). Both treatment groups had similar incidences of symptomatic and asymptomatic hypotension. These data demonstrate that early administration of nesiritide in the emergency department is a safe and effective treatment of heart failure.