OBJECTIVES: To describe utilization of Erythropoiesis-Stimulating Agents (ESAs) in critical care patients in U.S hospitals METHODS: A retrospective, observational study examined on-label and off-label utilization of epoetin alfa and darbepoetin alfa in critical care patients admitted to the intensive care unit (ICU) between January 2002- June 2004. Patients who had received at least one dose of an ESA and had a primary or secondary diagnosis for an FDA approved indication were identified. Patient demographic and clinical characteristics were analyzed using descriptive statistics.  Logistic regression models were used to identify potential predictors of off-label use. RESULTS: A total of 91,357 patients from 433 hospitals received at least one dose of an ESA in an ICU during the study period. Approximately 62% of patients received erythropoietic agents off-label. Off-label use in the ICU was more likely in teaching hospitals, in larger sized hospitals, in females, for certain physician specialties, and in different regions of the U.S., The longer the hospital stay, the less likely off-label prescribing occurred. CONCLUSIONS: Off-label use of erythropoietic agents was common in ICU patients. Multiple factors were associated with off-label use in the ICU. Further studies are needed to determine the causes or appropriateness of off-label use.