BACKGROUND: The relationship between quality of life (QofL) and anemia has been the subject of recent debates; it has been suggested that the QofL changes associated with the treatment of anemia of chronic kidney disease (CKD) or ESRD patients should not be used in making decisions to treat anemia in CKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study examines the relationship between Kidney Disease Quality of Life (KDQofL) questionnaire domains and hemoglobin (Hgb) levels in 1200 patients with stage 3, 4, and 5 CKD followed in seven centers. QofL measures were compared in a stepwise fashion for hemoglobin levels of <11, 11 to <12, 12 to <13, and > or =13. ANOVA was used to examine the relationship between QofL scores and Hgb level, age, CKD stage, and albumin level; a history of diabetes, congestive heart failure, or myocardial infarction; use of erythropoetic-stimulating agents (ESA); and the interaction of hemoglobin level and ESA. RESULTS: The results demonstrate that with increasing Hgb levels there is a statistically significant increase in all four physical domains, the energy/vitality domain, and the physical composite score of the SF-36, and the general health score on the kidney disease component of the questionnaire. The most dramatic improvements in these various domains occurred between the <11 and the 11 to 12 group. CONCLUSIONS: Higher Hgb levels are associated with improved QofL domains of the KDQofL questionnaire. These findings have implications for the care of CKD patients in terms of the initiation of and the Hgb target of ESA therapy.