BACKGROUND: Patients with end-stage renal disease (ESRD) often show lipid abnormalities that may promote atherosclerosis. Although the standard lipid marker is low-density lipoprotein cholesterol (LDL-C) in official recommendations, the need of fasting blood sampling has prevented routine screening for plasma lipids in hemodialysis patients. METHODS: We therefore evaluated the power of non-high-density lipoprotein cholesterol (non-HDL-C) in predialysis (non-fasting) serum as a predictor of cardiovascular mortality in a cohort of 525 hemodialysis patients. RESULTS: During the mean follow-up of 64 months, 120 deaths, including 44 fatal cardiovascular events, occurred. Patients in the highest tertile of non-HDL-C (137 to 285 mg/dL) had a significantly higher risk for cardiovascular mortality (HR, 3.065; 95% CI, 1.357 to 6.925; P = 0.007) [correction] in a univariate Cox analysis. The association between non-HDL-C and cardiovascular mortality remained significant in multivariate Cox models, which included HDL-C, age, gender, duration of hemodialysis, blood pressure, presence of diabetes mellitus, serum albumin, C-reactive protein, and body mass index. CONCLUSION: Non-HDL-C in predialysis serum was a significant and independent predictor of cardiovascular mortality in hemodialysis patients. Non-HDL-C may be a useful marker for risk assessment in routine practice, although predictive powers of this and the standard fasting LDL-C should be compared in future studies.