Introduction: There is an urgent need to check the efficacy of SARS-CoV-2 vaccination among hemodialysis patients who are known to have large abnormalities of acquired immunity and a catastrophic risk of death from COVID-19. Objectives: In this cross-sectional study, we aimed to assess the humoral response following vaccination with the BNT162b2 (BioNTech / Pfizer Comirnaty) vaccine. Patients and methods: We analyzed the titer magnitude of the IgG antibodies directed against SARS-CoV-2 spike antigen 14 to 21 days after the second dose of the BNT162b2 vaccine in a group of hemodialysis patients who have not been confirmed with SARS-CoV-2 infection yet, compared with HD patients with a history of COVID-19. A total of 126 hemodialysis patients were stratified based on evidence of a previous infection with SARS-CoV-2 confirmed by the detection of viral RNA or nucleocapsid-specific IgG antibodies. Results: S-antigen immune response with a median (interquartile range) antibody titer of 366 (193–691) AU/ml was seen in 87 of 91 infection-naïve hemodialysis patients (95.6%), and in 68 (74.7%), a strong humoral response was observed with an anti-S antibodies titer greater than 200 AU/ml. Older patients were less likely to develop a response to S-antibodies (P <0.001). The median (interquartile range) S-antigen antibody titer in 35 previously infected hemodialysis patients was over 12-fold higher than in infection-naïve hemodialysis patients: 4620 (1240–7820) AU/ml (P <0.001). There were no significant differences in S-antibody titer between symptomatic and asymptomatic previously infected hemodialysis patients. Conclusions: Our study demonstrated that the majority of hemodialysis patients achieved a high immunization rate after vaccination with BNT162b2. Whether this translates into protecting this population from COVID-19 requires further research.