<jats:sec><jats:title>Background</jats:title><jats:p>End-stage kidney disease substantially increases the risk of severe COVID-19. However, despite early robust immunogenicity of the mRNA-SARS-CoV-2 vaccination in patients with hemodialysis, the longevity of humoral response in this high-risk population is still unknown.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A prospective cohort study aimed to evaluate the longevity of serologic response in patients with hemodialysis, compared with a control group, 6 months following the second dose of the BNT162b2 vaccine. We assessed antibody response by quantitative measurement of IgG antibodies against the receptor-binding domain of the Spike protein (anti-S1-RBD IgG). Study outcomes were defined as a seropositivity rate and log-transformed anti-S1-RBD IgG levels at 6 months, and the change in antibody levels between 3 and 6 months.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>The cohort included 104 patients with hemodialysis and 84 controls. At a median time of 184 days (IQR, 183–188) following the second dose of the vaccine, 83/104 (79.8%) patients with hemodialysis maintained seropositivity for the anti-S1-RBD IgG level compared to 83/84 (98.8%) in the control group (<jats:italic>p</jats:italic> &lt; 0.001). The log-transformed antibody level was significantly lower in the hemodialysis group (2.23 ± 0.39 log AU/ml vs. 2.69 ± 0.65 log AU/ml, respectively, <jats:italic>p</jats:italic> &lt; 0.001). Older age and hypoalbuminemia were the only variables that were found to be associated with reduced log-transformed antibody levels in univariate and multivariate analysis. There was no interaction between dialysis status and an antibody-level decline rate (<jats:italic>p</jats:italic> = 0.972).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Among patients with hemodialysis, a seropositivity rate and anti-S1-RBD antibody titers were substantially reduced compared with a control group, at 6 months following the second dose of the BNT162b2 vaccine. These findings support the prioritization of patients with hemodialysis for a third “booster” dose.</jats:p></jats:sec>