On October 19, 2022, the U.S. Advisory Committee on Immunization Practices (ACIP) recommended the use of either a dose of 20-valent pneumococcal conjugate vaccine (PCV20) or 23-valent pneumococcal polysaccharide vaccine (PPSV23) as previously recommended for adults who have received 13-valent pneumococcal conjugate vaccine (PCV13) with an incomplete vaccination status. In addition, ACIP recommended shared clinical decision-making regarding administration of PCV20 for adults aged ≥65 years who completed their vaccine series with both PCV13 and PSPV23. A systematic review and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for evidence assessment and decision-making informed ACIP’s deliberations regarding use of PCV20.