OBJECTIVES: Pulmonary arterial hypertension (PAH) is a clinical condition that causes decreased exercise tolerance and heart failure. The aim of this study was to assess the cost-effectiveness of different drugs to manage PAH in adult, functional class III, patients, who have failed previously to calcioantagonists, from the health care payer’s perspective. METHODS: A five-state Markov model was performed to estimate one year costs and health consequences (1-month cycles). Effectiveness measures were quality-adjusted life years (QALY´s) gained, as well as reduction in hospital length of stay (LOS) and discontinuation rate due to adverse events. Transition probabilities were obtained from a meta-analysis involving national and international published literature. Doses of comparators used in the assessment were sildenafil (60 mg/day); bosentan (250 mg/day); sitaxsentan (100 mg/day) and ambrisentan (5 mg/day, reference alternative). Resource use and costs were obtained from hospital records (n=110) from the Social Security Mexican Institute. Costs include hospital stay, laboratory and respiratory function tests, imagenology, drugs and adverse events management. The model was validated according to international guidelines. Sensitivity analyses were performed employing bootstrapping techniques and acceptability curves were constructed. RESULTS: Per patient associated costs for sildenafil, bosentan, sitaxsentan and ambrisentan were [CI 95%]: US$16,840 [US$16,590 – US$17,176], US$38,068 [US$37,725 – US$38,497], US$40,203 [US$39,888 – US$40,647] and US$26,146 [US$25,898 – US$26,479], respectively. Sildenafil is associated to the highest gain in QALY´s: 0.1 [-0.01 – 0.22], as well as to the main reduction in discontinuation rate: 89.25 [89.11% - 89.4%] and reduction in LOS: 8.64 days [8.53 days – 8.75 days], respectively. In consequence, sildenafil represents the most attractive therapy to manage PHA in terms of cost-effectiveness. CONCLUSIONS: In the Mexican institutional setting, sildenafil demonstrated to be a cost-saving therapy to manage PHA in adult, functional class III patients. These results should be taken into account by Mexican health professionals to generate efficient resource allocation strategies.