OBJECTIVES: Pulmonary Arterial Hypertension (PAH) is a rare but life-threatening disease that entails a significant burden at the individual patient level. The objective of this study was to perform a cost of illness (CoI) analysis in order to investigate the direct cost of PAH, from a third party payer (EOPYY) perspective in Greece. METHODS: Resource utilization for “typical patient” scenarios, according to disease stage (severity), as defined by international guidelines, was elicited via Expert Opinion, by a panel of 13 physicians affiliated with major hospital units and clinics of the Greek NHS. Direct cost categories included the annual costs of patient monitoring (consultations, laboratory/diagnostic tests), medications and hospitalization. Cost calculations were based on the official EOPYY charges and tariffs and reported in Euros. RESULTS: The average annual direct cost per PAH patient is estimated at €49,130. Respective annual costs per patient, in line with WHO functional classification for PAH severity, are: €22,746.48 (WHO-FC I), €27,017.35 (WHO-FC II), €52,995.78 (WHO-FC III), and €99,602.24 (WHO-FC IV). Specialized pharmacotherapy was identified as the main cost driver, representing 97.29%, 96.46%, 91.14% and 82.29% of total FC-specific cost respectively. Total cost of pharmaceuticals (basic and specialized treatment) for all PAH patients, regardless of functional classification, is calculated at €13,752,623.12 per year (89.43% of the overall PAH cost in Greece). Hospitalization costs account for 9.18% of total disease cost, ranging from 0.48% of total annual cost in WHO-FC I patients to 16.77% in WHO-FC IV patients. CONCLUSIONS: PAH presents a significant burden to the national health system. The main part of total costs is attributed to pharmaceutical costs, a finding in line with the (few) available CoI studies for PAH in the international literature. Disease stage, as indicated by the WHO-FC, seems to be associated with remarkably higher costs, especially for severely ill (FC III and IV) patients.