OBJECTIVES: To compare dosing and treatment outcomes in patients with cancer receiving epoetin alfa (EPO) and darbepoetin alfa (DARB). METHODS: Records across several clinical and administrative data systems from adults receiving care in outpatient VA practice settings were reviewed. Eligible patients were required to have a cancer diagnosis, be =18 years, and have a record of treatment with EPO or DARB for anemia (hemoglobin (Hb) £11g/dL). RESULTS: A total of 2159 patients (1267 EPO, 892 DARB) were identified from November 2002 - August 2003. Baseline characteristics such as age, gender, weight, tumor type, percent receiving chemotherapy, baseline Hb, ECOG status, transfusion use, and iron supplementation across groups were all similar. Mean treatment duration was approximately 9 weeks (EPO: 57 days, DARB: 68 days). Mean weekly doses were: EPO 35,337 IU, DARB 108 mcg. Mean cumulative doses were: EPO 286,040 IU, DARB 1,036 mcg. Based on average wholesale price (AWP, Red Book 2003), weekly and cumulative treatment costs were lower for EPO (EPO: $472/week, $3820/episode; DARB: $539/week, $5170/episode; respectively). Hb change from baseline independent of observed transfusion was significantly greater for EPO compared to DARB at all assessments (Wk 4: 0.56 vs. 0.33 g/dL, p <0.0001; Wk 8: 0.76 vs. 0.46 g/dL, p <0.0001; Wk 12: 0.93 vs. 0.64 g/dL, p <0.0001; respectively). Cumulative hematologic effect, assessed by area under the Hb change curve, was also greater for EPO (7.2 vs. 4.5 g/dL). CONCLUSIONS: Results show greater early and overall hematologic outcomes with EPO compared to DARB at lower treatment costs suggesting dominance.