OBJECTIVES Recent changes to ESA prescribing information recommend initiation at Hb levels < 10 g/dL in cancer chemotherapy patients. Real world clinical and economic outcomes data associated with this initiation range for the two FDA-approved ESAs for this population [epoetin alfa (EPO) and darbepoetin alfa (DARB)] are sparse. METHODS Data collected between December 2003 and September 2008 from 61 U.S. oncology clinics from the Dosing and Outcomes Study of Erythropoietic Stimulating Therapies (D.O.S.E.) registry were assessed. Patients were included if they were initiated on ESAs at baseline (BL) Hb<10 g/dL, age >=18 years, and received >=2 doses of either EPO or DARB. Outcomes assessed included transfusion utilization, cumulative ESA doses, dose ratio (cumulative dose EPO: DARB) and ESA cost (based on cumulative ESA dose and December 2008 wholesale acquisition cost: EPO $13.77/1000 Units, DARB $4.818/mcg). RESULTS A total of 545 patients (237 EPO, 308 DARB) were included. BL characteristics were similar between treatment groups with regard to age, weight, cancer type and Hb. The mean administered dose was 42,610 Units in the EPO group and 259 mcg in the DARB group with a treatment interval of 11.6 days and 19.4 days, respectively. Mean treatment duration was similar between groups (~65 days, P=0.34). The proportion of patients transfused was similar between groups (~30%, P=0.70). Mean cumulative administered dose was 318,918 Units for EPO and 1,261 mcg for DARB corresponding to a dose ratio of 253:1 (Units EPO: mcg DARB). ESA cost was significantly lower in the EPO group compared to the DARB group (EPO: $4392, DARB: $6075; P<0.001). CONCLUSIONS In cancer chemotherapy patients with Hb <10g/dL prior to ESA initiation, transfusion utilization was similar between groups. However, ESA costs were 28% lower in the EPO group than the DARB group. These ESA-associated outcomes and cost data are informative to stakeholders treating cancer chemotherapy patients.