OBJECTIVES: Pulmonary arterial hypertension (PAH) is a chronic disease characterized by progressive elevation of pulmonary artery pressure and vascular resistance, leading to right-sided heart failure and premature death. The objective of the present research was to assess the clinical and economic aspects of current oral treatments options for PAH, New York Heart Association (NYHA) functional classes II and III, from the Brazilian Public Health System perspective. METHODS: A literature review was conducted on the efficacy and safety of ambrisentan, bosentan and sildenafil in patients diagnosed with PAH, in order to support the assumption of clinical equivalence between the treatments and the development of a cost-minimization analysis. The clinical outcome of interest was improvement in the distance (in meters) walked in 6 minutes (6MWD).  For the economic analysis, direct medical costs were considered. Treatment, diagnostic, and procedure costs were obtained from public price/reimbursement databases. Government acquisition prices were used for all drugs. Costs associated with adverse drug reactions and treatment withdrawals were also considered. A one-year time-horizon was used and all costs were presented in 2011 Brazilian currency (1BRL=0.60USD). RESULTS: There were no studies directly comparing any of the targeted agents. Thus, an indirect comparison of placebo controlled trials of selected PAH therapies was conducted. Standardized mean differences (SMD) between agents (over placebo) was calculated and the magnitude of effects between the comparators suggested similar clinical efficacy over 12–16 weeks of treatment. Confidence intervals of treatment effects overlapped substantially and supported the clinical assumption. The total annual/monthly costs for the interventions were R$13,169.76/R$1,097.48 for ambrisentan, R$13,226.86/R$1,102.24 for sildenafil, and R$30,227.70/R$2,518.98 for bosentan. CONCLUSIONS: Ambrisentan was identified as the alternative with the lowest cost and similar clinical outcomes compared with other selected therapies for treating patients diagnosed with PAH, NYHA functional classes II and III, under the Brazilian public perspective.