The use of nesiritide in the improvement of patient hemodynamics, decreased length of stay (LOS), and rehospitalization is discussed. Nesiritide is a useful agent for the treatment of the acutely decompensated heart failure patient. Previous trials suggest that the use of nesiritide results in improved outcomes as compared with other agents. To date, there are no data comparing nesiritide to milrinone in the treatment of the acutely decompensated heart failure patient. Fifty-five patients admitted to the heart failure service were identified retrospectively; 29 received nesiritide and 26 received milrinone. Baseline characteristics, hemodynamic data, and LOS data were collected. Primary outcomes were the overall LOS, intensive care LOS, and readmission within 30 days of discharge. Other outcomes included duration of vasoactive agents used, overall diuresis, and total cost of therapy. Baseline hemodynamic data were similar between groups. Patients in the milrinone group had an overall LOS of 8.2 days compared to 7 days in the nesiritide group (p = NS). LOS in the intensive care unit was 5.9 days in the milrinone group compared with 3.9 days in the nesiritide group (p = 0.007). Readmission at 30 days was 28% in the milrinone group compared with 16% in the nesiritide group (p = NS). Infusion time was shorter in the nesiritide group, 50 versus 117 hours (p = 0.001). Cost of therapy (cost of bed, supplies, and drug) was $398 less per patient receiving nesiritide. The use of nesiritide led to improvement in patient hemodynamics and resulted in a trend toward decreases in LOS and rehospitalization. Total cost of therapy was lower in the nesiritide group as compared to those patients treated with milrinone.