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Ongoing surveillance after pneumococcal conjugate vaccination (PCV) deployment is essential to inform policy decisions and monitor serotype replacement. We report serotype and disease severity trends in 3,719 adults hospitalized for pneumococcal disease in Bristol and Bath, United Kingdom, during 2006–2022. Of those cases, 1,686 were invasive pneumococcal disease (IPD); 1,501 (89.0%) had a known serotype. IPD decreased during the early COVID-19 pandemic but during 2022 gradually returned to prepandemic levels. Disease severity changed throughout this period: CURB65 severity scores and inpatient deaths decreased and ICU admissions increased. PCV7 and PCV13 serotype IPD decreased from 2006–2009 to 2021–2022. However, residual PCV13 serotype IPD remained, representing 21.7% of 2021–2022 cases, indicating that major adult PCV serotype disease still occurs despite 17 years of pediatric PCV use. Percentages of serotype 3 and 8 IPD increased, and 19F and 19A reemerged. In 2020–2022, a total of 68.2% IPD cases were potentially covered by PCV20.