OBJECTIVE Anemia during combination therapy with pegylated interferon alfa-2b plus ribavirin (RBV) for chronic hepatitis C virus (HCV) patients usually leads to RBV dose reduction or discontinuation. This study evaluated the effect of erythropoietin-beta (EPO-beta) to maintain RBV dose and hemoglobin (Hb) level in chronic HCV patients treated with antiviral combination therapy. METHODS Eighty-eight chronic HCV patients who developed anemia during therapy were enrolled into this retrospective study: 55 in the EPO-beta group and 33 in the untreated group. The study endpoints were to assess the RBV maintenance and the changes in Hb. RESULTS A higher percentage of patients with RBV maintenance was observed in the EPO-beta group compared with the untreated group (nadir Hb level <10.5 g/dL; 70% vs. 38%, P = 0.020; nadir Hb < 10 g/dL; 62% vs. 27%, P = 0.046). The mean Hb change from week 12 to week 20 was higher in the EPO-beta group when compared with the untreated group, especially for patients receiving a total EPO-beta dose of more than 16 000 U (+0.70 g/dL vs. -0.32 g/dL, P = 0.023) and of 10 000 U-14 000 U (+0.60 g/dL vs. -0.32 g/dL, P = 0.023). CONCLUSIONS Low-dose EPO-beta can maintain RBV dose and increase Hb levels in anemic chronic HCV patients receiving combination therapy.