Grading of Recommendations, Assessment, Development and Evaluation (GRADE) review of the evidence for benefits and harms for Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine for children aged 6 months­–­­4 years was presented to the Advisory Committee for Immunization Practices (ACIP) on June 18, 2022. GRADE evidence type indicates the certainty in estimates from the available body of evidence. Evidence certainty ranges from type 1 (high certainty) to type 4 (very low certainty) [1]. The policy question was, “Should vaccination with Pfizer-BioNTech COVID-19 vaccine (3 doses, 3 µg) be recommended for children 6 months–4 years of age during an Emergency Use Authorization?” The potential benefits pre-specified by the ACIP COVID-19 Vaccines Work Group included prevention of symptomatic laboratory-confirmed COVID-19 (critical), hospitalization due to COVID-19 (important), multisystem inflammatory syndrome in children (MIS-C) (important), and asymptomatic SARS-CoV-2 infection (important). The two pre-specified harms were serious adverse events (SAEs) (critical) and reactogenicity grade ≥3 (important). A systematic review of evidence on the efficacy and safety of a three-dose regimen of Pfizer-BioNTech COVID-19 vaccine among children aged 6 months–4 years was conducted. The quality of evidence from one Phase II/III randomized controlled trial was assessed using a modified GRADE approach [2]. A lower risk of symptomatic COVID-19 was observed with vaccination compared with placebo, but certainty in the estimate was very low (relative risk [RR]: 0.20; 95% confidence interval [CI]: 0.05, 0.77, evidence type 4). Immunobridging was also assessed in support of efficacy. In both age groups, 6–23 months and 2–4 years, the immune response to vaccine was non-inferior to that observed in young adults ages 16-25 years (6–23 months: GMR: 1.19; 95% CI: 1.00, 1.43; 2–4 years: GMR: 1.30; 95% CI: 1.13, 1.50; evidence type 2). The available data indicated that SAEs were balanced comparing vaccine and placebo recipients, but certainty in the estimate was low (RR 0.66; 95% CI: 0.38, 1.15; evidence type 4). One vaccine recipient had two SAEs which were considered potentially related by the investigator and FDA. FDA noted that the events were also consistent with viral myositis. Reactogenicity grade ≥3 was slightly higher in the vaccine group, but the confidence interval crossed the null (RR 1.20; 95% CI: 0.88, 1.64); evidence type 2). About 4.3% of vaccine recipients and 3.6% of placebo recipients reported any grade ≥3 local or systemic reactions following dose 1, dose 2, or dose 3.