A Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) review of the evidence for benefits and harms for Pfizer Respiratory Syncytial Virus (RSV) preF vaccine was presented to the Advisory Committee on Immunization Practices (ACIP) on June 21, 2023. GRADE evidence type indicates the certainty in estimates from the available body of evidence. Evidence certainty ranges from high certainty to very low certainty [1]. The policy questions were, “Should vaccination with Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose administered intramuscularly [IM]), rather than no vaccine, be recommended in persons aged ≥65 years?” and “Should vaccination with Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM), rather than no vaccine, be recommended in persons aged 60–64 years?” The benefits chosen by the ACIP RSV Vaccines Work Group (Work Group) as critical or important to policy decisions were prevention of RSV lower respiratory tract illness/disease (LRTI/LRTD) (critical), medically attended RSV LRTI/LRTD (critical), hospitalization for RSV respiratory illness (important), severe RSV respiratory illness requiring supplemental oxygen (O2) or other respiratory support (important), and death due to RSV respiratory illness (important). The harms chosen by the Work Group as critical or important to policy decisions were serious adverse events (critical), inflammatory neurologic events* (important) and reactogenicity grade ≥3 (important). A systematic review of evidence on the efficacy and safety of Pfizer RSVpreF vaccine among persons aged 60 years and older was conducted. The quality of evidence from one Phase 3 randomized controlled trial (RCT) and one Phase 1/2 RCT were assessed using the GRADE approach [2-4]. A lower risk of RSV LRTI† was observed with vaccination compared to placebo (incidence rate ratio [IRR] 0.156, 95% confidence interval [CI]: 0.048, 0.404, evidence certainty: moderate), corresponding to a vaccine efficacy of 84.4% (95% CI: 59.1%, 95.2%)§. This was observed over one complete RSV season (Season 1) and one partial second RSV season (Season 2). A lower risk of medically attended RSV LRTI¶ was also observed (IRR 0.191; 95% CI: 0.047, 0.563; evidence certainty: moderate), corresponding to a vaccine efficacy of 81.0% (95% CI: 43.5%, 95.2%)§. The trial was not powered to detect a lower risk of hospitalization for RSV respiratory illness (IRR 0.333; 95% CI: 0.006, 4.143; evidence certainty: very low) nor a lower risk for severe RSV respiratory illness requiring supplemental oxygen or other respiratory support** (IRR 0.000; 95% CI: 0.013, 78.33; evidence certainty: very low), corresponding to a vaccine efficacy of 66.7% (95% CI: -315%, 99.4%) and 0% (-7750%, 98.7%) for the outcomes, respectively. No deaths due to RSV respiratory illness were identified among vaccine recipients or placebo recipients. In terms of harms, the pooled available data from the Phase 3 and Phase 1/2 RCTs indicated that serious adverse events (SAEs)†† were balanced between the vaccine and placebo arms (risk ratio [RR] 1.041; 95% CI: 0.944, 1.148; evidence certainty: high). Reactogenicity grade ≥3§§ was similar between the vaccine and placebo arms of the trials (RR 1.43; 95% CI: 0.852, 2.385; evidence certainty: moderate), with 1.0% of vaccine recipients and 0.7% of placebo recipients reporting any grade ≥3 local or systemic reactions following injection. Three participants in the intervention group of the Phase 3 trial were reported to have inflammatory neurologic events within 42 days after vaccination (one case of Guillain-Barré syndrome [GBS], one case of Miller Fisher syndrome [a GBS variant], and one case of undifferentiated motor-sensory axonal polyneuropathy with worsening of pre-existing symptoms), compared with zero participants in the placebo group. No inflammatory neurologic events were reported in the phase 1/2 RCT.