OBJECTIVES: Oral therapies that target nitric oxide signaling (sildenafil) or endothelin signaling (bosentan and ambrisentan) are used to treat pulmonary arterial hypertension (PAH). We studied the treatment patterns, resource utilization, and costs associated with these three oral therapies in a US population of commercially insured patients. METHODS: This was a retrospective study using claims from a large health insurance database. Commercial and Medicare Advantage patients with claims indicating PAH between January 2006 and December 2008 and whose first PAH treatment was for ambrisentan, bosentan, or sildenafil were selected for study inclusion. PAH treatment patterns, PAH-related utilization, and PAH-related costs were assessed during a minimum 6 month follow-up period.  RESULTS: A total of 727 patients were identified for study inclusion. Sildenafil was the most common initial treatment (n=455 patients), followed by bosentan (n=251 patients) and ambrisentan (n=21 patients). On average, ambrisentan patients received one pill/day with a daily dose of 7mg, bosentan patients received 2 pills/day with a daily dose of 222mg, and sildenafil patients received 2.3 pills/day with a daily dose of 61mg. Approximately 44% of ambrisentan, 35% of bosentan, and 25% of sildenafil patients experienced a dose increase (p=0.013) during the follow-up period. PAH-related inpatient and emergency department utilization were similar among the groups, while ambulatory visits differed among the groups, with average monthly counts of 1.2, 0.8, and 0.5 visits for ambrisentan, bosentan, and sildenafil patients (p<0.001). Follow-up total PAH-related costs were significantly different among the groups, with average monthly costs of $6820, $5332, and $3632 for ambrisentan, bosentan, and sildenafil patients (p=0.020). Cost differences were primarily driven by PAH-related pharmacy costs, which were significantly lower in sildenafil patients (p<0.001).  CONCLUSIONS: Of the three oral PAH treatments studied, sildenafil was the most frequently prescribed, and was associated with lower pharmacy and overall costs than either ambrisentan or bosentan.