OBJECTIVES: To evaluate recent epoetin alfa (EPO) and darbepoetin alfa (DARB) drug utilization in CRC Medicare patients treated in the hospital outpatient setting. METHODS: An analysis of longitudinal medical claims in CRC Medicare patients using the Medicare 100% Institutional Database was performed to evaluate EPO and DARB utilization from 2005 to 2007.  Patients included had ≥ 1 non-myeloid cancer diagnosis, were ESA treatment naïve, received chemotherapy during the preceding or same quarter as ESA treatment, and received ≥2 doses of EPO or DARB.  Patients diagnosed with chronic kidney disease, myelodysplastic syndrome, treated with both agents within the same quarter, or received dialysis were excluded.  A treatment episode was defined as the time from the quarter of the first ESA dose to the quarter of the last ESA dose.  Mean cumulative ESA dose was used to calculate drug costs using April 2009 wholesale acquisition costs (EPO $14.44/1000 units; DARB $5.064/mcg). RESULTS: A total of 19,028 EPO and 29,130 DARB treated CRC patients were identified between 2Q2005 and 4Q2007.  The age distribution, the proportion of females, and the proportion receiving IV iron were similar between the groups.  The EPO group had a lower mean (SD) Charlson Comorbidity Score [5.1(3.2)EPO; 5.5(3.2)DARB, P<0.001].  Mean (SD) treatment duration was 1.9(1.1) quarters for EPO; 2.0(1.1) quarters for DARB (P value <0.001).  Mean (SD) cumulative dose was 356,800(357,700)units for EPO; 1,371(1230)mcg for DARB.  The observed dose ratio (EPO units/DARB mcg) was 260:1.  ESA drug costs per treatment episode were $5,153 for EPO and $6,944 for DARB.  Overall ESA drug costs were $1,791 higher (P <0.001) for DARB, representing a 35% higher cost compared to EPO.  CONCLUSIONS: This study of Medicare CRC patients treated with ESA in the hospital outpatient setting observed 35% higher ESA drug costs in patients treated with DARB compared to EPO.