Persistent pulmonary hypertension of the newborn (PPHN) occurs in 1-4% of neonates with transposition of the great arteries with intact ventricular septum (TGA/IVS). This association is often lethal. To our knowledge, only eight survivors have been described in the literature, two of whom benefited from extracorporeal membrane oxygenation (ECMO). We report two cases of PPHN complicating a TGA/IVS that were refractory to multiple therapies and resolved 48 hours after initiation of bosentan therapy. Bosentan, an oral dual endothelin-1 receptor antagonist, is a new treatment for pulmonary arterial hypertension that was both effective and safe in these two cases of TGA/IVS with PPHN. To our knowledge, it is the first use of bosentan in newborns.