OBJECTIVES: Few studies have examined the factors associated with the choice of route of administration of epoetin therapy among anemic hemodialysis patients. We conducted a cross-sectional study using data from the Centers for Medicare & Medicaid Services' End-Stage Renal Disease (ESRD) Clinical Performance Measures Project (CPM) to examine route of administration and anemia management strategies associated with receiving subcutaneous (SC) or intravenous (IV) epoetin. METHODS: Information was collected from 7630 patients receiving hemodialysis in October to December, 2000. Unadjusted associations were examined using t- and chi-square tests. Adjusted associations were estimated using logistic regression analyses. RESULTS: Use of SC route of administration varies widely across the United States. White, wealthier, incident to dialysis patients residing in the Midwest and West, and receiving dialysis in larger, hospital-based, not-for-profit independent facilities were more likely to receive SC epoetin. After controlling for patient sociodemographics and clinical history in a multivariate analysis, geography, profit status, and chain membership were the most significant predictors of route of administration. Hemodialysis patients in the Midwest and West were five and more than four times as likely compared to those in the Northeast (OR=4.94, CI 3.80, 6.42 and OR=4.34, CI 3.30, 5.70, respectively), and patients receiving dialysis from the only large not-for-profit chain were almost 6 times as likely compared to the largest for-profit chain (OR=5.88, CI 3.90, 8.85) to receive SC epoetin. CONCLUSION: Study findings indicate that clinical decision-making regarding route of administration for epoetin therapy appears to be influenced strongly by facility ownership and ESRD network in which a patient resides. Given the similar efficacy but significantly reduced epoetin dose associated with SC administration, these findings suggest an enormous lost opportunity for more efficient use of resources in the Medicare program.