Nonsteroidal anti-inflammatory drugs are widely used, but the potential hepatotoxic side effects are not always appreciated. Herein, we report the first case, to our knowledge, of an atopic patient in whom severe cholestatic jaundice from bile ductopenia developed 3 wk after initiation of ibuprofen therapy. This drug-induced vanishing bile duct syndrome is probably an immunological (hypersensitivity) reaction. Vanishing bile duct syndrome as a consequence of ibuprofen use should be considered as a potential cause of chronic cholestasis when other more common etiologies have been excluded.