Prostaglandin E1 (PGE1) is widely used in ductus-dependant congenital heart disease to maintain the patency of ductus. Hypertrophic pyloric stenosis (HPS) due to gastric mucosal proliferation is a rare complication of prolonged PGE infusion. A male newborn who developed HPS during PGE1 infusion is presented to discuss the clinical features and treatment modalities of PGE-related transient HPS. The boy was 2500 g and born at 35 weeks of gestation from a 23-year-old mother. He was admitted to neonatal intensive care with breathing difficulty and cyanosis. His echocardiography revealed pulmonary atresia, ventricular septal defect and major aorta-pulmonary collateral (MAPCA). PGE infusion with a dose of 0.05 mcg kg⁻¹ was initiated. At the 8th day of infusion, he developed non-billous vomiting. Ultrasonographic evaluation revealed 1.9 cm length of pyloric channel and 0.5 cm of wall thickness on 11th day and diagnosed as HPS. On 42th postnatal day, he underwent MAPCA closure, right modified Blalock-Taussi shunt and repair of pulmonary artery bifurcation with bovine patch. PGE infusion was stopped and enteral nutrition was started on 8th postoperative day. Control ultrasonography on 12th postoperative day revealed normal pyloric channel length (0.9 cm) and wall thickness (0.3 cm). Prolonged use of PGE infusion in neonates with congenital heart disease may cause transient HPS. The clinical and radiological features of HPS relieves after stopping PGE infusion. It should be kept in mind that HPS due to PGE infusion can be transient and pyloromyotomy should be kept for patients with persistent findings.