OBJECTIVES: Paragangliomas are rare neuroendocrine neoplasms of the head and neck. Treatment strategies include resection, definitive external beam radiation therapy (EBRT), stereotactic radiosurgery (SRS), or observation alone. Due to their rarity and indolent clinical behavior, the optimal management for long-term control is unknown. METHODS: This Institutional Review Board-approved retrospective study identified all paragangliomas of the head and neck treated with definitive fractionated radiotherapy at Duke University Medical Center from 1963 to 2005 with minimum 2-year follow-up. Local control (LC) was calculated using the Kaplan-Meier method. RESULTS: Thirty-one patients were identified and treated with EBRT (median dose: 54 Gy, range: 38-65 Gy). Twelve patients were treated with megavoltage photon; 19 were treated with either cobalt-60 or cesium-137. Fourteen (45%) had undergone resection preceding radiation. Median follow-up was 9 years (range: 2-35 years), with 10 patients having greater than 15-year follow-up. LC at 5, 10, and 15 years was 96%, 90%, and 90%, respectively. There were no failures in the group treated with megavoltage photons, although this was not statistically significant (P = 0.28). There was no difference in LC between salvage radiation therapy (RT) used after surgical failure and definitive RT alone (10-year LC, 73% vs. 100%, respectively, P = 0.31). The incidence of acute toxicity greater than grade 2 was 3%, and there were no late toxicities greater than grade 2. CONCLUSIONS: RT is an effective and well-tolerated treatment for paragangliomas of the head and neck.