Damage of large arteries is a major contributory factor to the high pulse pressure observed in patients with end-stage renal disease. Whether incremental modulus of elasticity (Einc), a classic marker of arterial stiffness, can predict cardiovascular mortality has never been investigated. A cohort of 79 patients with end-stage renal disease undergoing hemodialysis was studied between September 1995 and January 1998. Mean age at entry was 58+/-15 years. The duration of follow-up was 25+/-7 months, during which 10 cardiovascular and 8 noncardiovascular fatal events occurred. At entry, carotid Einc was calculated from measurements of diameter, thickness (echo-tracking technique), and pulse pressure (tonometry). Based on Cox analyses, 2 dominant factors emerged as predictors of all-cause and cardiovascular mortality: increased Einc and decreased diastolic blood pressure. Lipid abnormalities and the presence of previous cardiovascular events interfered to a smaller extent. After adjustment for confounding variables, the odds ratio for Einc >/=1 kPa-3 was 9.2 (95% confidence interval, 2.4 to 35.0) for all-cause mortality. These results provide the first direct evidence that in patients with end-stage renal disease undergoing hemodialysis, arterial alterations, as determined from carotid Einc, are strong independent predictors of all-cause and cardiovascular mortality.