OBJECTIVES: To compare the utilization of epoetin alfa (EPO) and darbepoetin alfa (DARB), 2 erythropoiesis-stimulating agents (ESAs), in chronic kidney disease (CKD) patients not receiving dialysis before and after the National Kidney Foundation/Kidney Disease Outcomes Quality Initiative (KDOQI) Anemia Treatment Guideline changes in March 2007.  METHODS: An analysis of medical claims from Ingenix IMPACT (2006-2008) and Medicare 5% (2006-2007) databases was conducted. Patients ≥18 years, newly initiated on ESAs, with ≥1 claim for CKD were included. Patients diagnosed with cancer, receiving chemotherapy or dialysis, or receiving both agents were excluded. Patients initiating ESA prior to March 31, 2007 were classified into the pre-guideline changes group and compared with patients initiating ESA after March 31, 2007 using the same time window prior and after KDOQI guideline changes. Dose per injection and cumulative dose evaluated up to 16 weeks after treatment initiation were compared.  RESULTS: A total 3427 patients were identified from both data sources. Following guideline changes, a lower number of patients initiated ESAs changes in the IMPACT database (1,059 pre- vs. 518 post-guideline changes) while the number of ESA-treated patient was more stable in the Medicare database (875 pre- vs. 975 post-guideline change). Among ESA-treated patients, the mean number of injections per patient decreased after the KDOQI guideline changes (pre- versus post-guideline changes: IMPACT—EPO: 4.0 vs. 3.8; DARB: 2.9 vs. 3.1; Medicare—EPO: 5.4 vs. 5.1; DARB: 4.9 vs. 4.6). Mean cumulative dose administered per patient also decreased post-KDOQI guideline changes [IMPACT—EPO Units: 95,147 vs. 86,898 (9% decrease) for pre- versus post-guideline changes, DARB mcg: 374 vs. 340 (9% decrease); Medicare—EPO Units: 104,739 vs. 103,265 (15% decrease), DARB mcg: 557 vs. 520 (4% decrease)].  CONCLUSIONS: This observational study suggests that the recent KDOQI guideline changes impacted the ESA utilization patterns in CKD patients not receiving dialysis.  A trend toward decreased ESA utilization was observed.