Peripheral artery stiffness is altered in diabetic patients with end-stage renal disease (ESRD), whereas few data exist to confirm this trend for proximal aortic stiffness. The pulse wave velocity of the proximal aorta (PWVr) and of the carotid-to-femoral aortic segment (PWVcf) were determined by ultrasound imaging in 160 patients with ESRD (70 diabetic) and in 160 matched control subjects. Also, plasma levels of endothelin, homocysteine, and high-sensitivity C-reactive protein were determined in both groups. Patients with ESRD had increased pulse pressure, left ventricular (LV) end-diastolic diameter, LV mass index, PWVr, and PWVcf compared with control subjects (p < 0.05). Diabetic patients had increased LV mass index, PWVr, and PWVcf compared with nondiabetic patients with ESRD (p < 0.05). Endothelin levels exhibited a strong relation with PWVr (r = 0.32, p < 0.001) and PWVcf (r = 0.33, p < 0.001) measurements in ESRD patients. Multivariate linear regression analysis revealed that age, diabetes, and plasma levels of endothelin were major determinants of increased PWVr measurements in the total ESRD population. After adjustment for age, body surface area, time on dialysis, systolic blood pressure, history of hypertension, and plasma endothelin levels, diabetes was an independent factor associated with PWVr in ESRD subjects. Diabetic patients with ESRD had significantly increased proximal aortic stiffness and significantly altered plasma levels of endothelin as compared with the nondiabetic.