Contrary to most examples of disparities in health outcomes, black patients have improved survival compared with white patients after initiating hemodialysis. Understanding potential explanations for this observation may have important clinical implications for minorities in general. This study tested the hypothesis that greater use of activated vitamin D therapy accounts for the survival advantage observed in black and Hispanic patients on hemodialysis. In a prospective cohort of non-Hispanic white (n = 5110), Hispanic white (n = 979), and black (n = 3214) incident hemodialysis patients, higher parathyroid hormone levels at baseline were the primary determinant of prescribing activated vitamin D therapy. Median parathyroid hormone was highest among black patients, who were most likely to receive activated vitamin D and at the highest dosage. One-year mortality was lower in black and Hispanic patients compared with white patients (16 and 16 versus 23%; P < 0.01), but there was significant interaction between race and ethnicity, activated vitamin D therapy, and survival. In multivariable analyses of patients treated with activated vitamin D, black patients had 16% lower mortality compared with white patients, but the difference was lost when adjusted for vitamin D dosage. In contrast, untreated black patients had 35% higher mortality compared with untreated white patients, an association that persisted in several sensitivity analyses. In conclusion, therapy with activated vitamin D may be one potential explanation for the racial differences in survival among hemodialysis patients. Further studies should determine whether treatment differences based on biologic differences contribute to disparities in other conditions. Copyright © 2008 by the American Society of Nephrology.