BACKGROUND: A respiratory syncytial virus (RSV) vaccination programme for older adults using bivalent pre-F vaccine was introduced in England from Sept 1, 2024. Although vaccine effectiveness has been reported against all-cause RSV-associated respiratory hospital admissions, data are scarce on vaccine effectiveness against different presentations of RSV-associated illness, such as exacerbation of chronic illness. METHODS: This multicentre, test-negative, case-control study used data from a national, hospital-based, acute respiratory infection sentinel surveillance (HARISS) system across 14 hospitals in England. Eligibility criteria were vaccine-eligible adults aged 75-79 years admitted to hospital with acute respiratory infection (ARI) for ≥24 h and tested with molecular diagnostic assays within 48 h of admission. Cases were RSV positive, and controls were negative for RSV, influenza, and SARS-CoV-2. Vaccination status and data on sex were obtained from the National Immunisation Information System. The primary outcome was hospital admission due to RSV-associated ARI, which was tested for using nasopharyngeal or combined nose and throat swabs. Clinical data were collected using a structured questionnaire. FINDINGS: Between Oct 1, 2024, and March 31, 2025, 1006 older adults were admitted to hospital with ARI; 173 were RSV positive (cases) and 833 were RSV negative (controls). 526 (52·3%) of 1006 individuals were female and 480 (47·7%) were male. Mean age was 77·8 years (SD 1·4) in individuals who were RSV positive and 77·6 years (SD 1·3) in those who were negative for RSV, influenza, and SARS-CoV-2. Vaccine effectiveness was 82·3% (95% CI 70·6-90·0) against hospitalisation for any RSV-associated ARI and 86·7% (75·4-93·6) in those with severe disease including oxygen supplementation. Vaccine effectiveness was 88·6% (75·6-95·6) among individuals admitted due to lower respiratory tract infection, including pneumonia, 77·4% (42·4-92·8) due to exacerbation of chronic lung disease, and 78·8% (47·8-93·0) due to exacerbation of chronic heart disease, lung disease, and/or frailty. In individuals with immunosuppression, vaccine effectiveness was 72·8% (39·5-89·3). INTERPRETATION: This study provides evidence that the RSV pre-F vaccine is highly effective against RSV-associated hospital admissions, including exacerbations of chronic disease, and in adults with immunosuppression. FUNDING: UK Health Security Agency.