Mediastinitis is a complication generally associated with thoracic surgery. Its occurrence after placement of a central venous catheter is uncommon, and only a few cases have been reported. An 83-year-old man who had mediastinitis due to extravasation of parenteral nutritional formula via a central venous catheter is presented. The signs and symptoms, diagnosis, and treatment of this unusual complication are described. This complication should be included in the differential diagnosis of mediastinitis in patients with a central venous catheter in place who have not had thoracic surgery.