In a prospective cohort study involving health care workers that was described previously,1 we evaluated the humoral response and vaccine effectiveness of a fourth dose of the BNT162b2 vaccine (Pfizer–BioNTech) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during a 6-month follow-up period in which omicron (mostly BA.1 and BA.2) was the predominant variant in Israel.2 The absence of previous SARS-CoV-2 infection was verified by SARS-CoV-2 testing and serologic followup testing (see Table S1 and the Supplementary Methods in the Supplementary Appendix, available with the full text of this letter at The humoral response (as assessed by the measurement of IgG and neutralizing antibodies) after receipt of the fourth vaccine dose was compared with that after receipt of the second and third doses. Vaccine effectiveness was assessed by comparing infection rates among participants who had received a fourth vaccine dose during various time periods (days 7 through 35, days 36 through 102, or days 103 through 181 after receipt of the fourth dose) with infection rates among those who had received three doses. Participants were to have received the third vaccine dose at least 4 months earlier. A Cox proportional hazards regression model was used, with adjustment for age, sex, and professional role; calendar time was used as the time scale to account for differences in the prevalence of infection over time (details are provided in the Supplementary Appendix). No participants died or were lost to follow-up.