BACKGROUND Inhaled treprostinil improved functional capacity as add-on therapy in the short-term management of patients with pulmonary arterial hypertension (PAH). This study investigated the long-term effects of inhaled treprostinil in patients concurrently receiving oral background therapy. METHODS A total of 206 patients (81% women) completing the 12-week double-blind phase of the Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension (TRIUMPH) study transitioned into an open-label extension. Patients were assessed every 3 months for changes in 6-minute walk distance (6MWD), Borg dyspnea score, New York Heart Association (NYHA) functional class, quality of life (QOL) scores, and signs and symptoms of PAH. RESULTS Patients were primarily NYHA class III (86%), with a mean baseline 6MWD of 349 ± 81 meters. A median change in 6MWD of 28, 31, 32, and 18 meters in patients continuing therapy was observed at 6, 12, 18, and 24 months, respectively. This effect was more prominent in those patients originally allocated to active therapy in the double-blind phase. Survival rates for patients remaining on therapy were 97%, 94%, and 91% at 12, 18, and 24 months, respectively. In addition, 82%, 74%, and 69% of patients maintained treatment benefit as evidenced by lack of clinical worsening at 12, 18, and 24 months. The most common adverse events were known effects of prostanoid therapy (headache [34%], nausea [21%], and vomiting [10%]) or were due to the route of administration (cough [53%], pharyngolaryngeal pain [13%], and chest pain [13%]). CONCLUSIONS Long-term therapy with inhaled treprostinil demonstrated persistent benefit for PAH patients who remained on therapy for up to 24 months.