Ibuprofen is currently widely prescribed in the pediatric population and has potentially very severe adverse events, even in the absence of an overdose. We treated a four year-old male who presented with severe jaundice, skin rash, xanthoma, eosinophilia and decreased hepatic function after overuse of ibuprofen for fever control. The liver biopsy revealed the vanishing bile duct syndrome. We report a case of vanishing bile duct syndrome associated with Ibuprofen overuse for the first case in Korea.