Bosentan, a dual endothelin-receptor antagonist, improved exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) in a randomized, double-blind, placebo-controlled trial. The study enrolled 213 patients with PAH (primary or associated with connective-tissue disease) and randomized them to receive placebo or bosentan (62.5 mg twice daily for 4 weeks, followed by 125 or 250 mg twice daily for 12 weeks). At week 16, patients treated with bosentan showed a significant improvement in six-minute walking distance (mean difference of 44 m from placebo, 95% CI 21 to 67; P<0.001). Bosentan also improved the Borg dyspnea index, WHO functional class, and increased the time to clinical worsening. The 125 mg dose was well tolerated, with no significant increase in adverse events compared to placebo. The 250 mg dose had a greater improvement in walking distance but also led to more frequent increases in liver aminotransferase levels. Bosentan significantly reduced the risk of clinical worsening and improved survival. The study demonstrated that bosentan is effective and well tolerated in patients with PAH, with the 125 mg dose being the preferred dose. The results confirm the therapeutic potential of endothelin-receptor blockade in PAH. The study had limitations, including the exclusion of patients with PAH secondary to other diseases and the lack of long-term survival data. Overall, bosentan significantly improves exercise capacity and delays clinical worsening in severe PAH.Bosentan, a dual endothelin-receptor antagonist, improved exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) in a randomized, double-blind, placebo-controlled trial. The study enrolled 213 patients with PAH (primary or associated with connective-tissue disease) and randomized them to receive placebo or bosentan (62.5 mg twice daily for 4 weeks, followed by 125 or 250 mg twice daily for 12 weeks). At week 16, patients treated with bosentan showed a significant improvement in six-minute walking distance (mean difference of 44 m from placebo, 95% CI 21 to 67; P<0.001). Bosentan also improved the Borg dyspnea index, WHO functional class, and increased the time to clinical worsening. The 125 mg dose was well tolerated, with no significant increase in adverse events compared to placebo. The 250 mg dose had a greater improvement in walking distance but also led to more frequent increases in liver aminotransferase levels. Bosentan significantly reduced the risk of clinical worsening and improved survival. The study demonstrated that bosentan is effective and well tolerated in patients with PAH, with the 125 mg dose being the preferred dose. The results confirm the therapeutic potential of endothelin-receptor blockade in PAH. The study had limitations, including the exclusion of patients with PAH secondary to other diseases and the lack of long-term survival data. Overall, bosentan significantly improves exercise capacity and delays clinical worsening in severe PAH.