OBJECTIVES: Investigate cost-effectiveness of sildenafil versus bosentan for treatment of pulmonary arterial hypertension (PAH) patients with WHO functional class (FC) II and III disease, in five European countries. METHODS: A decision-analysis model followed patients over 48 weeks through four health states: FC II, III, IV, and death. Model outcomes were: total treatment costs, quality-adjusted life-years gained, and incremental cost-effectiveness ratio Baseline demographics, transition probabilities and PAH-related mortality were based on data from 12 weeks of therapy in the SUPER-1 (sildenafil arms) and STRIDE-2 trials (bosentan arm). Utility values (SF36, EQ5D) for each health state were obtained from published sources and assumed to be equal between sildenafil and bosentan. Separate models were built for France, Italy, Germany, Spain and United Kingdom. Health resource use was estimated by interviewing local clinicians experienced in PAH. A base case analysis was conducted from the payer’s perspective which considered the direct costs of treatment. Unit costs were based on local tariffs and published data. To test the robustness of the results, univariate and probabilistic sensitivity analyses (PSA) were performed. RESULTS: Total treatment costs were significantly lower for sildenafil versus bosentan (cost differences range: €17.8k to €37.9k). Sildenafil dominated bosentan in each country. The key factor for this benefit was the lower acquisition cost of sildenafil. PSA indicated that the results were robust (cost difference: €17.6k to €36.7, 95% CI). Sensitivity analyses showed that the costs of treatment with sildenafil remained lower compared to bosentan when FC III patients received combination therapy (cost differences range from €11.95k to €25.8k). CONCLUSIONS: In the countries analyzed, sildenafil is a cost-effective treatment for patients with PAH. Limitations include lack of long-term data, use of open-label trial data (STRIDE-2), and that current practice includes therapeutic options such as combination therapy for which prospective clinical trial data are currently lacking.