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Background: Patients with left-ventricular dysfunction have an increased risk of developing heart failure after coronary artery bypass graft (CABG) surgery. Therapies to maintain cardiac output in such patients warrant investigation. Nesiritide is unique among intravenous medications used to manage heart failure. It mediates natriuresis and vasodilation and suppresses the reninangiotensin-aldosterone axis. Nesiritide may attenuate the body's neurohormonal response to myocardial stretch after CABG and provide clinical benefit in the immediate postoperative period., Objective: To determine whether perioperative infusion of nesiritide improves clinical outcomes compared with milrinone therapy., Methods: A prospective, open-label, randomized controlled trial was conducted in 40 consecutive hemodynamically stable patients with ejection fractions 35% or less undergoing CABG surgery. Patients were randomized to receive either an intraoperative bolus of nesiritide or milrinone followed by a 24 hour infusion of each agent. Length of postoperative intensive care unit stay was the primary outcome variable evaluated. Incidence of postoperative heart failure, 30 day readmission rates, mortality, and other clinical parameters were also compared., Results: Patients receiving nesiritide had a mean +/- SD postoperative intensive care unit stay of 50.6 +/- 46.8 hours compared with 44.1 +/- 23.5 hours in those receiving milrinone (p = 0.578). Incidence of postoperative heart failure was also not significantly different between the drugs (p = 0.259). Thirty day follow-up confirmed no difference in hospital readmission rates between nesiritide and milrinone (p = 0.661). No differences in mortality were observed during hospitalization or 30 days of follow-up., Conclusions: Nesiritide does not decrease postoperative intensive care unit stay or other clinical parameters compared with milrinone in high-risk patients with hemodynamically stable left-ventricular function undergoing CABG surgery.