Purpose: High-dose external radiotherapy used in the treatment of head and neck carcinoma has been implicated as a risk factor for accelerated atherosclerotic disease of the carotid arteries. However, how radiotherapy affects atherosclerotic disease is controversial, and little data exist to demonstrate a strong relationship between radiotherapy and progressive carotid disease. Methods: We performed a retrospective chart review of 69 patients (all men) who underwent duplex ultrasound scanning examinations for carotid disease between 1993 and 1998. Twenty-three patients had received high-dose radiotherapy for the treatment of head and neck carcinoma within the past 12 years (group 1; mean age, 67.8 years), and 46 patients were randomly selected as age-matched control subjects (group 2; mean age, 68.3 years). The mean radiation dose was 6060 ± 182 rads, and the average interval between radiotherapy and ultrasound scanning was 6.5 ± 1.8 years. There was no significant difference between the two groups in the presence of these comorbidities: diabetes mellitus, coronary artery disease, hypertension, tobacco use, hypercholesterolemia, peripheral vascular disease, or stroke. Similarly, there was no difference in the indications for the duplex scanning studies. Results: Five of the 23 patients in group 1 (21.7%) were found to have advanced carotid disease (70% to 99% stenosis); four patients were symptomatic, three patients went on to endarterectomy, and one patient was awaiting surgery. Two of the 46 patients in the control group (4%) had advanced carotid disease. One patient was symptomatic, and both patients underwent endarterectomy. A significant difference in the prevalence of advanced disease between the two groups was noted (P = .037). Sixteen patients who survived irradiation underwent a second duplex scanning study and had evidence of progressive disease with significant increases in peak systolic velocities. Conclusion: High-dose radiotherapy to the head and neck region may be a significant risk factor for accelerated carotid atherosclerotic disease. Routine carotid duplex surveillance may be warranted in this high-risk patient population.