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Background There are currently three Food and Drug Administration approved endothelin receptor antagonists (ERAs): bosentan, ambrisentan, and macitentan. There is a growing body of evidence that demonstrates the beneficial effects of ERAs in patients with pulmonary arterial hypertension (PAH). Objectives To compare the available evidence from randomized clinical trials for specific outcomes of different endothelin antagonists for the treatment of PAH. Methods A multi-database search of randomized controlled trials up to March 15, 2016 was conducted for those that would measure functional parameters of patients with PAH treated with ERA monotherapy versus placebo. Studies that analyzed 6-min walking distance, pulmonary vascular resistance, pulmonary arterial pressure, or WHO functional status were incorporated for analysis. A total of 15 trials and 2 subanalyses were compiled and quality and abovementioned outcomes were compared among studies. Results A constant decrease in pulmonary vascular resistance and pulmonary arterial pressure was globally reported among the different studies, resulting in increased 6-min walking distance and functional status compared to placebo. Conclusions Although this evidence clearly shows the benefit of ERAs, studies, which compare ERAs against one another and with other therapies for progressive PAH, have been lacking. Larger and longer studies are necessary to define the role of ERAs as standalone agents and in combination therapies., Author(s): Michael Kuntz[sup.1] , Miguel M. Leiva-Juarez[sup.2] , Suvitesh Luthra[sup.3] Author Affiliations: (1) Massachussets General Hospital, Boston, MAUSA (2) Department of Pulmonary Medicine, MD Anderson Cancer Center, Houston, TXUSA (3) [...]