We describe here an infant girl with ductal dependent complex cyanotic heart disease, who required prostaglandin infusion for a total of five months prior to Blalock-Taussig shunt procedure. Her alkaline phosphatase activity was raised after seven weeks being on prostaglandin and only dropped to the normal range seven days after discontinuing prostaglandin infusion. During our review at five months old, her limbs were grossly swollen and radiographic examination showed dense periosteal reaction in the long bones. Based on the clinical findings and investigations, she was diagnosed to have cortical hyperostosis, which is an uncommon side effect of prostaglandin. She underwent right Blalock-Taussig Shunt procedure successfully with no major complications. Unfortunately, she succumbed to infection two months after surgery.