Pulmonary artery thrombosis is rarely reported in preterm neonates. Although treatment of neonatal thrombosis remains controversial, thrombolytic agents must be considered when the thrombosis is life threatening. We herein present a case of a preterm newborn with pulmonary artery thrombosis accompanied by acute-onset respiratory failure and cyanotic congenital heart disease. The thrombosis was successfully treated using tissue plasminogen activator. In conclusion, the thrombolytic therapy should be considered in treatment of patients in whom the thrombosis completely occludes the pulmonary arteries.