Clostridium difficileinfection (CDI) is the most common cause of hospital-acquired diarrhea. A limited number of studies have looked at the risk factors for recurrent CDI. Mitochondrial NeuroGastroIntestinal Encephalopathy (MNGIE) is a rare multisystemic disorder that causes gastrointestinal dysmotility. Herein we present a patient with MNGIE who suffered recurrent and severeC. difficileinfection despite appropriate treatment. We aim to bring the gastroenterologist’s attention to gastrointestinal dysmotility as a possible risk factor for the development of recurrent or severe forms ofC. difficileinfections.