Background Fetuin A, a circulating inhibitor of ectopic calcification, is downregulated in hemodialysis and has been shown to predict cardiovascular mortality in this setting. The association of altered calcium-phosphorus with serum fetuin A levels is still a matter of debate. Although carotid intima-media thickness (cIMT) is a strong predictor of major cardiovascular events, its association with serum fetuin A levels is poorly defined. Study Design Cohort study. Participants & Settings 174 uremic patients on long-term hemodialysis therapy enrolled in 4 university hospitals. Predictors Serum fetuin A levels at the beginning of the study (T0) and after 12 months (T12). Outcomes Progression of atherosclerosis assessed by means of cIMT measurements at 24 months (T24); cardiovascular morbidity and mortality at 36 months. Results Serum fetuin A concentrations at T0 and T12 were 282.3 ± 79.4 and 290.0 ± 92.2 μg/mL, respectively. Mean T0 and T24 cIMT values were 1.02 ± 0.2 and 1.06 ± 0.2 mm, respectively ( P < 0.001). Fatal and nonfatal cardiovascular disease occurred in 36 and 86 patients by 36 months, respectively. In multivariate logistic regression, higher calcium-phosphorus product was associated with lower serum fetuin A level (odds ratio, 0.96; 95% confidence interval CI, 0.93 to 1.00; P = 0.02). Multiple regression analysis showed that T0 serum fetuin A level was associated with T24 cIMT ( P = 0.01) after adjustments for age, cholesterol level, high-sensitivity C-reactive protein level, previous cardiovascular events, and T0 cIMT. In a multivariate Cox regression analysis, cardiovascular mortality was independently associated with a 1-tertile lower T0 serum fetuin A level, and a 1-tertile higher T0 cIMT value was independently associated with greater cardiovascular mortality (hazard ratio, 0.45; 95% CI, 0.15 to 0.65; P = 0.007 and hazard ratio, 10.00; 95% CI, 3.16 to 31.73; P < 0.001, respectively) after adjustment for age and previous cardiovascular events. Limitation Length of follow-up. Conclusion Calcium-phosphorus product in hemodialysis patients inversely correlated with serum fetuin A level, which, in turn, was associated inversely with progression of atherosclerotic lesions and cardiovascular mortality in this study population.