Sickle cell trait (HbAS) associates with impaired urinary concentration, hematuria, and renal papillary necrosis, but its prevalence among African Americans with ESRD is unknown. We performed a cross-sectional study reviewing available hemoglobin phenotypes for 188 of 206 adult African-American patients receiving renal replacement therapy in four dialysis units. Results from the state newborn screening program in corresponding counties provided the local population prevalence of sickle trait among African Americans. Compared with the general African-American population, HbAS was twice as common among African Americans with ESRD (15% versus 7%, P < 0.001). Prevalence of hemoglobin C trait (HbAC) was similarly more common (5% versus 2%, P < 0.01). The higher prevalence of HbAS and HbAC in the ESRD population raises the possibility that these hemoglobinopathies contribute to a decline in kidney function, either alone or in conjunction with other known risk factors for renal disease. The potential effect of HbAS on the development and progression of CKD and its effect on the course and management of patients with ESRD deserve further study.