In the last years, the number of hemodialysis (HD) patients with erythropoietin (rHuEPO) resistance is increasing. Probably, central venous catheters (CVCs) contribute to this resistance by inducing inflammation and oxidative stress. This study was aimed to compare vitamin E-bonded dialyzer (PSVE) versus polyethersulfone membrane. Sixteen subjects with CVCs were included in a prospective two-arm crossover 12-month study. The primary endpoints were the rHuEPO requirement and the erythropoiesis-stimulating agents (ESA) index, which was defined by the ratio between weekly EPO dosage (IU/kg/week) and Hb levels (g/dl). The mean dosages of rHuEPO to maintain hemoglobin between 10.5 and 12 g/dl were 135 ± 59 and 101 ± 57 IU/kg/week with polysulfone and PSVE, respectively (P = 0.14). The ESA indexes were 12.1 ± 5.2 and 8.7 ± 5.2 (P < 0.0001) with polysulfone and PSVE, respectively. A trend towards consensual changes in protein glycoxidation, antioxidant, and inflammatory markers was observed. In conclusion, the study suggests a role for PSVE in the reduction of ESA index in HD patients with CVCs.