Although HIV-associated pulmonary hypertension and primary pulmonary hypertension (PPH) are clinically and histologically similar, treatment options for the former are limited. Treatment with calcium channel blockers (CCB), proven to be beneficial in a subset of patients with PPH, has been disappointing in HIV-associated pulmonary hypertension and there are no data examining the effects of long-term epoprostenol in this entity. Six patients with severe HIV-associated pulmonary hypertension were treated with continuous intravenous epoprostenol infusions. Acute infusion of epoprostenol resulted in a significant (p < 0.05) decrease in mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) of 16. 4 and 32.7%, respectively, and a significant (p < 0.05) increase in mean cardiac output (CO) of 36.9%. At 1 yr, mean PAP and PVR had decreased by 21.7 and 54.9% (p < 0.05), respectively, and mean CO had increased by 51.4% (p < 0.05) when compared with baseline values. Repeat catheterizations of three patients at 2 yr and one patient at 40 mo demonstrated further improvement or maintenance of hemodynamics. In addition, NYHA functional class improved in all patients. We conclude that epoprostenol infusion is effective in improving hemodynamic and functional status in this cohort of six patients with HIV-associated pulmonary hypertension acutely and long-term.