Recent data demonstrate a possible mortality benefit in traumatically injured patients when given subcutaneous recombinant human erythropoietin (rhEPO). The purpose of this report is to examine the effect of rhEPO on mortality and transfusion in burn patients. We conducted a review of burn patients (greater than 30% total body surface area, intensive care unit [ICU] days greater than 15) treated with 40,000 u rhEPO over an 18-month period (January 2007 to July 2008). Matched historical controls were identified and a contemporaneous cohort of subjects not administered rhEPO was used for comparison (NrhEPO). Mortality, transfusions, ICU and hospital length of stay were assessed. A total of 105 patients were treated (25 rhEPO, 53 historical control group, 27 NrhEPO). Hospital transfusions (mean 13,704 +/- mL vs. 13,308 +/- mL; P = 0.42) and mortality (29.6 vs. 32.0%; P = 0.64) were similar. NrhEPO required more blood transfusions (13,308 +/- mL vs. 6827 +/- mL; P = 0.004). No difference in mortality for the rhEPO and NrhEPO (32.0 vs. 22.2%; P = 0.43) was found. Thromboembolic complications were similar in all three groups. No effect was seen for rhEPO treatment on mortality or blood transfusion requirements in the severely burned.