A Grading of Recommendations, Assessment, Development and Evaluation (GRADE) review of the evidence for benefits and harms for GSK Respiratory Syncytial Virus (RSV) PreF3 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. The policy questions were, “Should vaccination with GSK RSVPreF3 vaccine (120µg antigen + AS01E adjuvant, 1 dose administered intramuscularly [IM]), rather than no vaccine, be recommended in persons aged ≥65 years?” and “Should vaccination with GSK RSVPreF3 vaccine (120µg antigen + AS01E adjuvant, 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 GSK RSVPreF3 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]. Efficacy findings were based on analyses of data collected during May 2021–March 2023, which included two complete RSV seasons for Northern Hemisphere participants and one complete RSV season for Southern Hemisphere participants. A lower risk of RSV LRTD† was observed with vaccination compared to placebo (incident rate ratio [IRR] 0.254, 95% confidence interval [CI]: 0.165, 0.379, evidence certainty: moderate), corresponding to a vaccine efficacy of 74.6% (95% CI: 62.1%, 83.5%)§. A lower risk of medically attended RSV LRTD¶ was also observed (IRR 0.225; 95% CI: 0.110, 0.421; evidence certainty: moderate), corresponding to a vaccine efficacy of 77.5% (95% CI: 57.9%, 89.0%).** The trial was not powered to detect a lower risk of hospitalization for RSV respiratory illness or severe RSV respiratory illness requiring supplemental oxygen or other respiratory support (for both outcomes IRR 0.236; 95% CI: 0.005, 2.112; evidence certainty: very low), corresponding to a vaccine efficacy for both outcomes of 76.4% (95% CI: -111%, 99.5%). 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 participants in the vaccine and placebo arms (risk ratio [RR] 1.019; 95% CI: 0.908, 1.145; evidence certainty: high). Reactogenicity grade ≥3§§ was associated with vaccination (RR 4.099; 95% CI: 1.989, 8.446; evidence certainty: high), with 3.8% of vaccine recipients and 0.9% of placebo recipients reporting any grade ≥3 local or systemic reactions following injection. No inflammatory neurologic events were observed within 42 days after injection in either placebo-controlled trial. However, inflammatory neurologic events were observed in other trials not included in the GRADE assessment due to lack of an unvaccinated comparator: one event of Guillain-Barré syndrome (GBS) reported within 42 days after vaccination in a recipient of the investigational vaccine in an open label trial without a placebo arm and two events of acute disseminated encephalomyelitis (ADEM) reported within 42 days after coadministration of the investigational vaccine with standard dose seasonal influenza vaccine in a coadministration study (for one of these ADEM cases the investigator revised the diagnosis to hypoglycemia and dementia in June of 2023).