Objective Continuous IV epoprostenol (prostacyclin) therapy improves survival and quality of life in patients with pulmonary arterial hypertension (PAH). IV epoprostenol therapy may be limited by serious complications related to the need for an implanted central venous catheter, and its chemical instability and short half-life. Treprostinil is a longer-acting prostacyclin analog, chemically stable, and suitable for continuous subcutaneous administration. We report successful transitioning to subcutaneous treprostinil of patients who presented with life-threatening complications of IV epoprostenol delivery. Design Open, uncontrolled study. Setting ICUs and departments of cardiology at academic hospitals. Patients Eight patients with PAH treated with continuous IV epoprostenol. Intervention Transition to subcutaneous treprostinil following an empiric protocol. Results Transition to treprostinil was achieved successfully in 21 to 96 h, with no major adverse side effects, and no change in the improved clinical status achieved with IV epoprostenol. Doses of epoprostenol before transition ranged from 3.5 to 75 ng/kg/min (mean, 27 ng/kg/min). Doses of treprostinil at completion of the transition ranged from 3 to 65 ng/kg/min (mean, 22 ng/kg/min). Four to 11 months later, the patients remained clinically improved. In spite of mild-to-moderate infusion site pain, all patients reported an improved sense of comfort and well-being. Conclusion Patients with PAH can be safely transitioned from treatment with IV epoprostenol to subcutaneous treprostinil.