Mediastinitis is a rare but a serious complication of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). We present 3 cases of mediastinitis following these diagnostic procedures. In 2 of the patients oropharyngeal bacteria were found in the cultures from the mediastinal abscess. All 3 cases were treated successfully with thoracotomy and drainage of the abscess together with intravenous antibiotics. On the basis of these cases and an updated review of the literature we discuss the most likely etiology for mediastinitis in association with EBUS-TBNA and EUS-FNA procedures and propose how to reduce the risk for this serious complication. The possibility of mediastinitis should always be kept in mind when a patient complains of fever over a long period of time as well as chest pain and malaise after an EBUS-TBNA or EUS-FNA procedure.