The effects of recombinant human erythropoietin (r-HuEPO) administration on adequacy of hemodialysis (HD) during single-use versus multiple-reuse of hemophan hollow-fiber dialyzers were assessed in 16 stable end-stage renal disease (ESRD) patients. After 12 months of r-HuEPO treatment and maintenance HD with low-flux single-use dialyzers, in the same group of ESRD patients the effectiveness of automated dialyzer reprocessing using peroxyacetic acid was evaluated. Comparison between r-HuEPO-treated patients dialyzed with single-use devices and those treated with reused dialyzers revealed no significant differences in urea kinetic modelling and nutritional status. However, the duration of HD and heparin dosage were significantly (p < 0.05) increased, and the number of dialyzer uses was properly limited during the reuse program. When dialyzer reprocessing was performed, the r-HuEPO dosage and hemoglobin level remained unchanged if compared with the subgroup treated with single-use dialyzers. It was demonstrated that r-HuEPO treatment did not affect the adequacy of HD, even in case of dialyzer reuse.