We report a case of portal vein thrombosis (PVT) in a term neonate following an exchange transfusion through an umbilical vein catheter which was left in situ for 16 h after the transfusion. The baby made a complete recovery after successful thrombolysis with regional streptokinase infusion. To our knowledge, this is the first reported case of a PVT following an indwelling portal venous catheter left in situ with complete resolution following thrombolysis with regional streptokinase infusion.