The difficulty maintaining hemoglobin (Hgb) within the targets recommended by KDOQI is widely recognized. While factors responsible for erythropoietin resistance have been widely studied, factors responsible for the marked fluctuations and the inability to maintain Hgb within the target range have only begun to be investigated. This study was a cross-sectional review of anemia management in hemodialysis patients. The purpose was to evaluate factors responsible for Hgb decreases of 0.5 or 1.0 g/dL and to determine the primary factors responsible for Hgb decreases below 11 g/dL. Hgb values and clinical events were extracted from patient management databases between January 1, 2005 and November 30, 2006. Isolated events were defined as events that occurred at least 30 days after any previous event and had Hgb measurements within 2 weeks before and after the event. Increasing hospital length of stay and surgical access intervention were the most common events that resulted in a decrease in Hgb. The most common factor present in patients with Hgb decreases below 11 g/dL was the withholding of recombinant human erythropoietin (rHuEPO) within the preceding 2 months. This was the only explanation for the decrease in Hgb to <11 g/dL in 38.5% of such events. The ability to maintain dialysis patients' Hgb in the target range is complicated by intervening acute events that require hospitalization or surgical access interventions. The withholding of rHuEPO appears to be a major factor in Hgb decreases below 11 g/dL.