Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is prevalent worldwide, and effective and safe vaccines against this virus have been developed. Although trends in antibody titers after vaccination and/or SARS-CoV-2 infection have been reported, long-term studies with high frequency of measurements are limited. This report describes the long-term and detailed trends in the antibodies against SARS-CoV-2 S protein receptor-binding domain (S-RBD) measured repeatedly after vaccination and/or infection in 3 healthcare workers. All healthcare workers were administered 30 µg of the messenger RNA vaccine, BNT162b2, during all vaccinations. The peak value of the SARS-CoV-2 S-RBD titer was reached at 1–2 weeks after vaccination and then decreased by half within 8 weeks after vaccination; the peak values of the antibody titer increased with repeated vaccinations. In contrast, after SARS-CoV-2 infection, the peak value of the antibody titer was reached at 4–8 weeks after infection, and the antibody titer remained elevated up to 16–40 weeks after the peak. This report describes the long-term and detailed trends in the anti-SARS-CoV-2 S-RBD titers, showing different patterns after vaccination and/or SARS-CoV-2 infection.