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Introduction: Patients with inflammatory bowel disease (IBD) receiving immunosuppressive therapy might have an increased risk of developing a severe course of SARS-CoV-2 infection. The aim of this study was to investigate the development of antibodies in immunosuppressed patients with IBD compared to a healthy control group and to determine the effect of immunomodulators on the level of anti-SARS-CoV-2 IgG antibody levels before and after a third vaccination against SARS-CoV-2., Methods: This is a single-center study with a retrospective observational design. Seventy-one IBD patients matched by propensity score to 71 healthy employees (control group) were included. Blood was taken from both groups at predetermined times before and after the third booster vaccination., Results: All patients with IBD (n = 71, 100%) received immunomodulatory therapy. The mean antibody level before the third vaccination was 1,352.88 U/mL (SD = 1,011.489) in the IBD group and was not lower compared to the control group (p = 0.088). Gender, age, and disease duration had no significant impact on the development of antibody levels. Patients with TNF-alpha blockers had significantly lower antibody titers (p = 0.011) compared to the control group. Patients with integrin inhibitor therapy had significantly higher antibody titers (p = 0.003) than the controls. After the third vaccination, an increase in antibody titers was recorded in all patients in the IBD group., Conclusion: We recorded an antibody titer in all patients with IBD that was not significantly lower compared to healthy controls despite immunomodulatory therapy. The booster vaccination led to an increase in antibody levels in all patients with IBD., (© 2024 S. Karger AG, Basel.)