Objective: Little data exist to support the durability of thoracic endovascular repair during prolonged periods of follow-up. This study examines the durability and long-term results with the Zenith TX1 and TX2 thoracic devices (Cook Inc, Bloomington, Ind) in high-risk patients. Methods: Data were collected prospectively from 2001 to 2007 on high-risk patients who presented with thoracic aneurysms, chronic aortic dissection, or fistulas treated with a Zenith thoracic device. Surgical modifications of proximal or distal landing zones were performed when necessary. Computed tomography follow-up scans were performed before discharge, at 1, 6, and 12 months, and yearly thereafter. Three-dimensional reconstruction software with central line of flow measurements was used to assess aortic morphologic characteristics. Kaplan-Meier analysis was used to assess survival, freedom from reintervention, predictive factors of poor outcome, and morphologic changes, including aneurysm sac behavior. Results: A total of 160 patients (44% women; mean age, 70) were treated for 130 thoracic aneurysms, 25 aortic dissections with aneurysm, 2 fistulas, and 3 symptomatic or aortic ruptures, or both. Mean follow-up was 36 months, and aneurysm size was 67 mm. Seventy-five patients (47%) had undergone prior aortic aneurysm repair. Surgical modifications were required to create adequate landing zones in 33% patients, including 28 elephant trunk/arch reconstruction, 22 carotid-subclavian bypasses, and seven visceral vessel bypasses. Iliac conduits were required in 31 patients. Early mortality (<30 days) occurred in 11 patients (6.9%). Overall mortality at 1 year was 16%. Aneurysm sac increase (>5 mm) requiring intervention was observed only in one patient in the settings of component separation and type III endoleak that was treated; the sac is now stable. Twenty-seven endoleaks were detected in 25 patients: 15 primary endoleaks (9.4%) <30 days and 12 secondary endoleaks (7.5%) >30 days. Secondary interventions were required in 42 patients (26%). Conclusion: Endovascular treatment of thoracic aortic pathologies with the Zenith TX1 and TX2 devices is feasible and durable. The mid- to long-term results are encouraging, with acceptable low reintervention rates and with good survival within high-risk patients.