Background: It seems that more erythropoietin (EPO) is required when given intravenously (IV) than when given subcutaneously (SC). Estimates of the magnitude of this difference vary widely, impeding development of economic models in this area. Concerns about pure red cell aplasia led our program to switch from SC to IV EPO, so we studied the impact of this change on the cost of anemia therapy. Methods: All in-center hemodialysis patients who had received EPO for at least 3 months prior to and following conversion to IV EPO were studied. Data was obtained retrospectively for 1 year prior to and prospectively for 1 year following conversion. The costs of anemia therapy (EPO, transfusions and iron) were calculated from the hospital’s perspective. Results: 158 patients were studied. One month after switching, the hemoglobin fell significantly, reaching a nadir at 3 months. This triggered more use of EPO, iron and transfusions. By month 7 hemoglobin levels had returned to initial levels, with a median rise in EPO dose of 1,250 units/week (p < 0.001). After the switch, the median rise in total anemia therapy costs was 13.1% (CAD 665/patient-year, p < 0.01). Conclusions: Conversion of EPO from SC to IV dosing increased the costs of anemia therapy at our center.