The objective of the study was to quantify the direct and indirect incremental costs of epoetin alpha (EPO) therapy for anemia in pre-dialysis chronic kidney disease (CKD). Using employer claims data from January 1998 to January 2005, direct (medical and pharmacy) and indirect (sick leave and disability) costs were compared between CKD-anemic patients treated with EPO before dialysis (n = 199) and those not treated with an erythropoiesis-stimulating therapy (EST) (n = 196). Among the results, incremental direct and indirect cost savings for EPO-treated patients were $1443 and $328 per member per month (PMPM) (p < 0.001), respectively, compared to non-EST-treated patients with anemia. After multivariate adjustments, direct and indirect costs remained significantly lower by $852 and $308 PMPM (p < 0.001), respectively, for the EPO-treated group. Direct costs during the first 6 months of dialysis also were significantly lower for the EPO-treated group (who received EPO before dialysis), by $1515 PMPM (p = 0.0267, in multivariate regression). In conclusion, anemic CKD patients treated with EPO before dialysis had significantly lower direct and indirect costs compared to non-EST-treated patients.