Stevens-Johnson syndrome (SJS) is a serious and potentially life-threatening disease. Vanishing bile duct syndrome (VBDS) is a rare cause of progressive cholestasis. Both syndromes are mostly related with drugs. We report a case of a patient withciprofloxacin-induced SJS and acute onset of VBDS,and reviewed the related literature. It is the first case of ciprofloxacin-induced VBDS successfully treatedwith tacrolimus. This case reminds physicians of the importance of drug reactions, their severity, techniques for diagnosis and methods of management.