Background: Most incident hemodialysis (HD) patients who initiate dialysis therapy with anemia usually can achieve a hemoglobin (Hb) level of 11 g/dL or greater (<110 g/L) within a few months of the initiation of recombinant human erythropoietin (EPO) therapy. However, patients unable to achieve this level may be at greater risk for adverse outcomes. Whether intractable anemia is a modifiable problem or a marker for other conditions is unclear. This question was addressed in a cohort of 130,544 incident HD patients from 1996 to 2000 who were administered EPO regularly. Methods: Medicare claims data were used to determine demographic characteristics, comorbidities, hospitalizations, and related events. Patients who did not achieve an Hb level of 11 g/dL or greater (<110 g/L; n = 19,096; 14.6%) during months 4 to 9 after dialysis therapy initiation were compared with those who did. Results: Patients unable to achieve an Hb level of 11 g/dL (110 g/L) were younger and more often of nonwhite race. In addition, these patients had more comorbid conditions; experienced more hospitalizations with longer stays, more infectious hospitalizations, and more catheter insertions; and were administered more blood transfusions. EPO was administered in higher and increasing doses during the years of study among patients with intractable anemia compared with those with an Hb level of 11 g/dL or greater (<110 g/L), likely denoting increasing attempts to correct anemia over the years. Conclusion: It is apparent that incident HD patients unable to achieve an Hb level of 11 g/dL or greater (<110 g/L) have a greater disease burden. The independent association of intractable anemia with such future outcomes as cardiovascular events and hospitalizations remains to be determined.