Epoetin-alfa (EA) and darbepoetin-alfa (DA) are agents for treating anemia in dialysis patients. In September 2005, our free-standing outpatient hemodialysis center (community-hospital based) implemented an interchange from EA to DA. Since then, all hemodialysis patients receive DA as the preferred agent. We performed this observational study to compare effectiveness of DA with EA in anemia management in a cohort of hemodialysis outpatients. We studied 98 hemodialysis outpatients who received twice to thrice weekly EA from January to August 2005. These patients were switched to DA in September 2005, and baseline DA dose was calculated from the conversion table in the package insert. After a 4 month titration phase, the same cohort of patients, now on once weekly DA, was followed from January to September 2006. Dose of EA or DA was adjusted to maintain hemoglobin at 11 to 13 g/dL. Hematologic and dialysis parameters were collected on a monthly basis, and inpatient data were excluded. Mean ± standard deviation age was 65.8 ± 14.2 years, with 42 (42.9%) women. Mean ± standard deviation hemoglobin level was 12.5 ± 1.6 g/dL during EA and 12.5 ± 1.6 g/dL during DA therapy (P = 0.23). Proportion of patients achieving hemoglobin (11-13 g/dL) was 44.5% ± 28.9% with EA and 49.8% ± 25.8% with DA (P = 0.09). Average intrapatient absolute hemoglobin variability was 1.0 ± 0.5 g/dL on EA and 1.1 ± 0.5 g/dL on DA (P = 0.29). Median (and interquartile range) EA dose used was 11,400 (7,050-22,800) IU/week, and median DA dose was 59.8 (40-91.6) mcg/week with an EA:DA dose conversion ratio of 191:1. Patients on EA or DA had similar dialysis adequacy, albumin, and iron parameters. DA is as effective as EA in treating anemia in hemodialysis outpatients. Dose requirement of DA is greater than 200:1 of the amount of EA and may not translate into cost savings.