OBJECTIVES:  Selexipag is the only oral PAH therapy targeting the prostacyclin pathway approved in Europe. In a long-term outcome-driven phase III trial, selexipag was shown to reduce the risk of events of the composite morbidity/mortality (M/M) endpoint versus placebo. A model was developed to investigate the cost-effectiveness of the addition of selexipag versus inhaled iloprost in patients already receiving an endothelin receptor antagonist (ERA) and a phosphodiesterase type 5 inhibitor (PDE-5i). METHODS: In the individual patient simulation model, the risk of morbidity, mortality and severe adverse events were modeled. Morbidity events lead to a deterioration in health status (e.g., functional class) and subsequently a higher M/M risk and lower utility. Inhaled iloprost is a non-invasive treatment alternative also targeting the prostacyclin pathway; however, data supporting its long-term efficacy or use in combination with ERAs and PDE-5is are not available. A conservative assumption of equal efficacy to selexipag was made. Patient characteristics, risk of morbidity, mortality and severe adverse events were taken from the phase III study. Drug, procedure and adverse event costs were based on publicly available data. The analysis was done from the societal perspective with a life time horizon. A 3% discounting rate was applied for costs and benefits. One-way and probabilistic sensitivity analyses were performed. RESULTS:  Selexipag was found to be cost-effective (base-case ICER: 37,350 SEK/QALY) due to improved health outcomes (0.88 QALYs) with slightly higher costs (33,032 SEK). In the probabilistic sensitivity analysis, selexipag had a 77.4% probability of being cost-effective at a threshold of 500,000 SEK/QALY. Sensitivity analyses found the results to be most impacted by the disutility associated with inhaled iloprost administration and the mortality and M/M risks associated with selexipag and inhaled iloprost. CONCLUSIONS:  Selexipag was found to be cost-effective versus inhaled iloprost in patients already receiving an ERA and a PDE-5i in Sweden.