OBJECTIVES: PAH therapy has evolved over the past decade, increasing in complexity and in evidence for efficacy. The 2015 ESC/ERS Guidelines recommend that patients stabilized on monotherapy should receive additional therapy if treatment goals are not met; however the cost of this addition has yet to be quantified. This study compared healthcare resource utilization and costs in the 30 days preceding and following the addition of the second medication class. METHODS: Patients who initiated monotherapy with endothelin receptor antagonists, phosphodiesterase-5 inhibitors, or soluble guanylate cyclase stimulators between 2010 and 2014 and had ≥2 medical claims with diagnoses for PAH or PAH-related conditions (portal hypertension, connective tissue disease, congenital heart disease, HIV) were identified in the Truven Health MarketScan Commercial and Medicare Supplemental Databases. Patients who added a second medication class whilst remaining on the initiating class were selected. The first pharmacy claim for the second medication class was defined as the sequential combination therapy initiation (SCTI) date. McNemar’s and paired t-tests were used to compare healthcare utilization and costs in the 30-days pre-SCTI date and 30-days post-SCTI date (including the SCTI date). The analysis compared PAH-related sub-totals, for which only claims with a PAH diagnosis or prescription were included. RESULTS: Non-pharmacy PAH-related medical costs for patients meeting study criteria (n=172) increased significantly from $1,740 in the pre-SCTI period to $2,929 in the post-SCTI period (p=0.038).  Total PAH-related costs, including pharmacy, were significantly different (pre $5,052 vs. post $15,791, p<0.001).  Total all-cause costs, including pharmacy, also increased post-SCTI (pre $9,044 vs. post $20,012, p<0.001). Non-pharmacy all-cause medical costs were not significantly different (pre $5,294 vs. post $6,676, p=0.337). All-cause and PAH-related inpatient admissions and emergency room visits were rare. CONCLUSIONS: Rising PAH-related costs when adding the second medication class suggests that physicians may be responding to disease progression with treatment escalation.