BACKGROUND: In late summer, 2024, the UK introduced the maternal bivalent respiratory syncytial virus (RSV) prefusion F (RSVpreF) vaccine for all pregnant individuals at a gestation of 28 weeks or more. After an initial catch-up phase, the maternal RSVpreF programme transitioned to year-round delivery, and in late summer, 2025, nirsevimab replaced palivizumab for infants at high risk of severe RSV disease. We aimed to estimate the protection provided by maternal RSVpreF against hospital admission with RSV in infants up to the age of 6 months, and to assess the overall performance of the UK RSV prevention programme once this had entered a steady state. METHODS: We conducted a national, multicentre, prospective, test-negative, case-control study at 37 BronchStop hospital sites in the UK. Patient and public involvement from a group of parents informed study protocol design. Included patients were prospectively enrolled infants aged 6 months or younger at the time of hospital admission with acute lower respiratory tract infection (ALRI) and tested for RSV. Test-positive infants (case patients) were defined as those admitted with a positive RSV test. Test-negative infants (control patients) were defined as those who tested negative for RSV. Infants were followed up until hospital discharge or death while an inpatient. The primary outcome was infant hospital admission with RSV-associated ALRI in infants born at a gestation of 28 weeks or more who did not receive nirsevimab postnatally. Primary vaccine effectiveness was calculated with the use of a conditional logistic regression model adjusted by site, calendar month of attendance, gestational age at birth, socioeconomic status, age at admission, and breastfeeding status. This study was registered with ClinicalTrials.gov, NCT04959734. FINDINGS: Between Sept 2, 2025, and Jan 31, 2026, 1356 infants were admitted to participating sites and screened for eligibility, 694 of whom were included in the primary analysis (429 RSV-positive infants and 265 RSV-negative infants). Median age was 2·2 months (IQR 1·3-3·9) for RSV-positive infants and 1·7 months (1·0-3·3) for RSV-negative infants. 394 (57%) of 694 infants were male and 300 (43%) were female. Ethnicity data were available for 693 mothers, of whom 538 (78%) identified as being of White ethnicity. The mothers of 161 (38%) RSV-positive infants and 175 (66%) RSV-negative infants had received the RSVpreF vaccine before delivery. The adjusted vaccine effectiveness of maternal RSVpreF vaccination for preventing infant hospital admission was 61% (95% CI 38-75) for infants aged up to 6 months, and 76% (54-87) for infants aged up to 3 months. The overall effectiveness of the UK RSV prevention programme was 61% (39-75) through to age 6 months. INTERPRETATION: In the real-world setting of the UK's maternal vaccination programme, RSVpreF vaccination was effective up until the age of 6 months in reducing the risk of hospital admission with RSV-associated ALRI, as was the UK's infant RSV prevention programme. These data could help decision makers to evaluate whether RSVpreF or an anti-RSV infant monoclonal antibody best serves the needs of their infant population. FUNDING: National Institute for Health and Care Research, The Wellcome Trust, Imperial College London, the Public Health Agency Northern Ireland, the Belfast Health and Social Care Trust Charitable Trust Funds, the Edinburgh Children's Hospital Charity, and the Respiratory Syncytial Virus Consortium in Europe.