The BREATHE-5 study demonstrated that bosentan, an oral endothelin receptor antagonist, provides clinical benefits in patients with Eisenmenger's syndrome. As a result, the European Medicines Agency (EMEA) approved its use for this indication. However, follow-up in that study was limited to 16 weeks and patients with complex congenital heart disease were excluded. We assessed the effect of long-term bosentan treatment in 10 patients with complex congenital heart disease and Eisenmenger's syndrome. In the mean clinical follow-up period of 25 months, all patients reached the target dose without developing side effects and without experiencing a change in arterial oxygen consumption at either rest or maximal exercise. Moreover, there were significant changes in clinical parameters: NYHA functional class improved from 3.3+/-0.7 to 2.5+/-0.9 (P=.002) and the 6-minute walk distance increased from 266+/-161 m to 347+/-133 m (P=.015).