The effect of hospitalization on an ESRD patient’s hemoglobin (Hgb) level and erythropoietin (Epo) requirement has not been investigated. We postulated patients with end stage renal disease required an increased Epo dose to maintain stable Hgb during hospitalization and for a period following discharge. To evaluate this hypothesis, we conducted a retrospective chart review on 65 hemodialysis patients. All hemodialysis patients admitted for more than 2 days who did not have more than the index hospitalizations for 2 months prior to and following discharge were included. Multiple parameters including Hgb, Epo dose, intravenous iron dose, serum iron, TIBC, and ferritin during the 2 months before and the two months after hospitalization, Hgb at admission and discharge, Hgb trough, surgery, blood transfusions and co-morbid factors were evaluated. Statistical significance was evaluated using ANOVA or rank-sum testing, as appropriate. In 65 hemodialysis patients (24 M/41 F, age 58 ± 2.2 years, mean ± SEM), Hgb levels following discharge and for 2 subsequent months were significantly lower than 2 months prior to admission (11.4 ± 0.25 vs. 10.7 ± 0.22 g/dl, p < 0.01). This occurred in spite of an increase in Epo dose (128 ± 14 vs. 185 ± 21 U/kg/week, p < 0.0001) over this 2-month period. There was no difference in the iron saturation before and after hospitalization (22 vs. 23%,p > 0.05). There were also no apparent effects of comorbid factors, including surgery, or discharge diagnosis on the changes in Hgb or Epo requirements. However, patients who required a blood transfusion during the hospitalization had lower Hgb levels and higher Epo doses both prior to and after hospitalization, as well as lower Hgb trough levels. In addition, females had lower Hgb levels than males both prior to and after hospitalization, and were receiving a higher Epo dose 191 ± 18 vs. 129 ± 20 U/kg/week at 1 month and 215 ± 18 U/kg/week vs. 134 ± 22, p < 0.005 at 2 months after hospitalization. Conclusion: This study points out that hemodialysis patients experience a significant and prolonged decrease in Hgb levels after hospitalization, even despite a moderate increase in Epo dosing.