BACKGROUND Extra-adrenal catecholamine-secreting tumors are referred to as paragangliomas. We reviewed our experience with mediastinal paragangliomas treated at Mayo Clinic over the last 30 years. METHODS Fourteen patients were identified who had resection of a mediastinal paraganglioma between 1973 and 2007. Perioperative data obtained from the medical record and follow-up information were reviewed. RESULTS The median age of patients at operation was 39 years (range, 27 to 68 years), 71% were female, and all had a history of hypertension. Preoperative diagnosis of a catecholamine-secreting tumor was confirmed through elevated 24-hour urinary norepinephrine in 12 patients and tumor location was determined with metaiodobenzylguanidine scintigraphy, computed tomography or magnetic resonance imaging scans in the majority. The tumor was adjacent to the heart or great vessels in all patients and was resected through a median sternotomy (n = 10), or with posterolateral thoracotomy (n = 4). In 6 patients, cardiopulmonary bypass was used to facilitate dissection of the paraganglioma from the heart or great vessels. There was one intraoperative death in this series due to blood loss. Ten of the 11 patients were alive at follow-up (median follow-up: 2.3 years; range, 0 to 19.4 years). Symptoms of catecholamine excess were eliminated or greatly improved in all patients who had a functioning tumor preoperatively, but 6 of these patients were still being treated with antihypertensive medications. CONCLUSIONS Functional paragangliomas can be diagnosed with measurement of fractionated catecholamines and metanephrines; mediastinal localization is determined with appropriate scanning techniques. These tumors can be treated successfully by surgical resection with modest surgical risk, often necessitating cardiopulmonary bypass, with good long-term survival. Hypertension may persist even after complete resection of the tumor.