Hemoglobin (Hgb) levels fluctuate in patients with end-stage renal disease over time. This study quantified Hgb level variability and the likelihood of falling within the Hgb level goal range of 11 to 12 g/dL. Implications on the percentage of patients exceeding 3-month rolling average Hgb levels of 12, 12.5, and 13 g/dL were determined. Phase I (n = 65,009) tracked patients with Hgb values initially outside the goal range ( 12 g/dL) during 2000. Correlation with facility-specific thresholds also was evaluated. Phase II (n = 48,133) quantified variation in 3-month rolling average Hgb levels in a subset with greater than 10 months of data (mean Hgb, 11.4 +/- 1.3 g/dL). A total of 24,948 patients (38.4%) had Hgb levels between 11 and 12 g/dL. In only 8% did Hgb levels consistently remain less than 11 g/dL, and in 18%, greater than 12 g/dL all year. Twenty-nine percent (18,633 patients) moved from below to above target range or vice versa. Greater mean facility Hgb level correlated with a greater percentage of patients with Hgb levels greater than 10 g/dL (R2 = 0.49) and greater than 12.5 g/dL (R2 = 0.61). For facilities to have 90% or greater of patients with 3-month rolling average Hgb levels greater than 10 g/dL, 13% to 31% of patients will have 3-month rolling average Hgb values greater than 12.5 g/dL. The average individual patient is expected to have a +/-1.4-g/dL fluctuation in 3-month rolling average Hgb levels per year. Despite increased mean Hgb levels and erythropoietin (EPO) and iron use, the spread of the Hgb distribution curve remained unchanged in the last 6 years. Variability caused by laboratory assays, biological factors, and therapeutic response determines patient Hgb level variability. Improving factors that can be manipulated (eg, standardizing EPO and iron algorithms) and adjustment of the target Hgb level range, specifically, by increasing the upper bound, likely will decrease the observed variability and further enhance the quality of anemia management. Copyright 2003 by the National Kidney Foundation, Inc.