This study prospectively examined the hypothesis that dividing stable dialysis patients into different clinical subsets by presence or absence of coronary disease equivalent will lead to clearer risk stratification by abnormal troponins and highly sensitive C-reactive protein (hs-CRP). Patients with end-stage renal disease have an annual mortality of 18%. Previous studies have shown that elevated cardiac troponins T and I and hs-CRP predict increased mortality, although these studies have not taken clinical parameters into account. Stable patients with end-stage renal disease (n = 173) were divided into 2 groups: 115 patients with coronary disease equivalent (known coronary or peripheral vascular disease or diabetes mellitus) and 58 patients without it. The 2 groups were then stratified by biomarkers (cardiac troponins T and I and hs-CRP) and followed for 27 months. The primary outcome was all-cause mortality. Patients with coronary disease equivalent had twofold greater annual mortality than those without (20.4% vs 9.8%, p = 0.003). Among patients with coronary disease equivalent, those with elevated troponins had a further increase in the risk for death relative to patients with normal troponins (25% vs 9% with cardiac troponin I elevation, p <0.001; 24% vs 12% with cardiac troponin T elevation, p = 0.04). hs-CRP did not add to the risk stratification of patients with coronary disease equivalent. Conversely, in patients without coronary disease equivalent, neither troponin further predicted the risk for death. In the small subset of patients without coronary disease equivalent who had hs-CRP ≥3 mg/L, mortality was significantly increased (p = 0.01). In conclusion, initial clinical assessment, followed by the addition of biomarkers, can be used to risk-stratify stable patients with end-stage renal disease.