African Americans experience a higher mortality rate and an excess burden of ESRD compared with Caucasians in the general population, but among those treated with dialysis, African Americans typically survive longer than Caucasians. We examined whether differences in inflammation may explain this paradox. We prospectively followed a national cohort of incident dialysis patients in 81 clinics for a median of 3 years (range 4 months to 9.5 years). Among 554 Caucasians and 262 African Americans, we did not detect a significant difference in median CRP between African Americans and Caucasians (3.4 versus 3.9 mg/L). Mortality was significantly lower for African Americans versus Caucasians (34% versus 56% at 5 years); the relative hazard was 0.7 (95% CI, 0.5 to 0.9) after adjusting for age, gender, dialysis modality, smoking, body mass index, diabetes, BP, cholesterol, cardiovascular disease, congestive heart failure, comorbid disease, hemoglobin, albumin, CRP, and IL-6. However, the risk varied by CRP tertile: the relative hazards for African Americans compared with Caucasians were 1.0 (95% CI, 0.7 to 1.4), 0.7 (95% CI, 0.4 to 1.3), and 0.5 (95% CI, 0.3 to 0.8) in the lowest, middle, and highest tertiles, respectively. We obtained similar results when we accounted for transplantation as a competing event, and we examined mortality across tertiles of IL-6. In summary, racial differences in survival among dialysis patients are not present at low levels of inflammation but are large at higher levels. Differences in inflammation may explain, in part, the racial paradox of ESRD survival.