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The aim of this study was to report a case of neonatal migratory polycyclic erythema of urticaria associated with alprostadil. A full-term male neonate with complex heart disease was diagnosed. The patient had a Taussig-Bing anomaly, transposition of the great arteries (TGA), large subpulmonic ventricular septal defect (VSD), large patent ductus arteriosus (PDA), severe coarctation and interrupted aortic arch. The patient developed an adverse drug reaction during alprostadil infusion. Following the reaction, alprostadil was administered at sequentially reduced doses, and the patient eventually became tolerant of alprostadil. The patient successfully continued therapy with no further reactions or recurrences. No adverse drug reactions developed during infusion until the patient was discharged from the hospital and was transferred to a tertiary care hospital for cardiothoracic surgery.