Calcifying atherosclerosis is an active process, which is controlled by calcification inhibitors and inducers. Fetuin-A, an acute phase glycoprotein, is one of the more powerful circulating inhibitors of hydroxyapatite formation. A prospective multicenter cohort study was initiated to include both hemodialysis (HD) and peritoneal dialysis (PD) patients in an evaluation of the association of serum fetuin-A levels with both cardiovascular (CV) and non-CV mortality. An increase in the serum fetuin-A concentration of 0.1 g/l was associated with a significant reduction in all-cause mortality of 13%. There was a significant 17% reduction in non-CV mortality and a near significant reduction in CV mortality. This association of fetuin-A and mortality rates was comparable in both HD and PD patients even when corrected for factors, including but not limited to age, gender, primary kidney disease, C-reactive protein levels, and nutritional status. We conclude that serum fetuin-A concentrations may be a general predictor of mortality in dialysis patients.