<b><i>Introduction:</i></b> In this study, we examined the effect of switching dialysis membranes on the response to influenza virus vaccination in HD patients. <b><i>Methods:</i></b> This study consisted of two phases. In phase 1, antibody titers were measured and compared between HD patients and healthy volunteers (HVs) before and after vaccination against influenza virus. Using antibody titers 4 weeks after vaccination, HD patients and HVs were classified according to seroconversion (i.e., antibody titers against all four strains were &#x3e;20-fold) or non-seroconversion (i.e., antibody titer against at least one strain was &#x3c;20-fold). In the phase 2, we examined whether the change in the dialysis membrane from a polysulfone (PS) to a polymethyl methacrylate (PMMA) membrane affected the response to vaccination in HD patients without seroconversion in response to the vaccine the previous year. Patients with seroconversion and non-seroconversion were classified as responders and nonresponders, respectively. Additionally, we compared clinical data. <b><i>Results:</i></b> In the phase 1, 110 HD patients and 80 HVs were enrolled, and their seroconversion rates were 58.6% and 72.5%, respectively. In the phase 2, 20 HD patients without seroconversion in response to the vaccine the previous year were enrolled, and the dialyzer membrane was changed to PMMA 5 months before annual vaccination. After annual vaccination, 5 and 15 HD patients were categorized as responders and nonresponders, respectively. In the responders, β2-microglobulin, white blood cell counts, platelet counts, and serum albumin levels (Alb) were all higher than in the nonresponders. <b><i>Conclusion:</i></b> The responsiveness to vaccination against influenza virus was lower in HD patients compared with HVs. Changing the dialysis membrane from PS to PMMA appeared to affect the response to vaccination in HD patients.