Milrinone is a phosphodiesterase inhibitor that has been shown to improve hemodynamic parameters in patients with class III to IV heart failure when administered intravenously for < or =48 hours. This study examines the tolerability of long-term intravenous milrinone therapy and assesses its utility in allowing upward titration of oral vasodilator agents. A retrospective review of hospital records identified 63 patients who underwent hemodynamic monitoring and received intravenous milrinone for >24 hours in a critical care setting. Hemodynamics and medications were recorded before and after 24 hours of milrinone therapy. Additional medications, as well as any adverse events, were recorded throughout milrinone therapy. The mean dose of milrinone was 0.43 +/- 0.10 microg/kg/min, with a mean duration of 12 +/- 15 days (range 1 to 70). Therapy was continued for >48 hours in 89% of patients. After 24 hours of milrinone therapy, patients exhibited significant improvements in pulmonary artery pressures, pulmonary capillary wedge pressures, and cardiac index. When compared with baseline, significantly more patients received angiotensin-converting enzyme (ACE) inhibitors after 24 hours of milrinone and at the end of milrinone therapy (67% vs 86%, p <0.01). Likewise, significantly more patients also received oral hydralazine and/or nitrates at the end of milrinone therapy (38% vs 65%, p <0.01) when compared with baseline. The mean doses of most oral medications at the 3 time periods were similar. The ACE inhibitor dose was significantly higher at the end of milrinone therapy when compared with baseline, and hydralazine dose was significantly higher at the end of therapy when compared with 24 hours. Few adverse effects were noted, with only 10% of patients experiencing symptomatic ventricular tachycardia and 2 patients with significant hypotension requiring discontinuation of the drug. The adverse events were similar in the group of patients who received milrinone for > or =7 days compared with the entire cohort. Milrinone was well tolerated over the long term in a controlled inpatient setting, and allowed uptitration of oral vasodilator therapy.