Premature infants with preterm premature rupture of membranes (PPROM) are at high risk of severe respiratory failure because of lung hypodysplasia associated with persistent pulmonary hypertension of the newborn (PPHN). We describe the clinical course of a 28-week gestation infant with PPROM from the 20th week and prolonged oligohydramnios before delivery, who developed refractory hypoxia treated with oral bosentan as adjunct therapy to inhaled nitric oxide (iNO) and oral sildenafil. Conclusion Our experience suggests that bosentan can be used in the premature infant with PPHN after PPROM. To the best of our knowledge, this is the first report of bosentan treatment in a premature infant.