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Background: In this phase 3 trial of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine (RSVPreF3-Mat), a higher rate of preterm birth was observed in the vaccine (6.8%) versus the placebo group (4.9%). Trial enrollment and vaccination were stopped. Results of investigations into this safety signal were reported previously. Here, we describe end-of-trial efficacy, immunogenicity, and safety results., Methods: Women 18-49 years old were randomized 2:1 to receive one dose of RSVPreF3-Mat (n=3557) or placebo (n=1771) at 240/7-340/7 weeks' gestation. Primary outcomes were any and severe medically assessed RSV-associated lower respiratory tract disease (MA-RSV-LRTD) in infants until 6 months post-birth and safety until 12 months post-birth. Other efficacy outcomes were evaluated, along with immunogenicity (until 6 months post-partum/birth) and safety in mothers and infants., Results: Efficacy in infants until 6 months post-birth was 65.5% (95% credible interval: 37.5-82.0) against any MA-RSV-LRTD, 69.0% (33.0-87.6) against severe MA-RSV-LRTD, and 50.1% (-3.6-75.8) against RSV hospitalization; it waned over time thereafter. Efficacy against MA-RSV-LRTD was 47.8% (-25.8-77.3) in low- and middle-income and 75.9% (46.1-91.5) in high-income countries. RSVPreF3-Mat induced a substantial increase in RSV-A neutralization titers in mothers, with efficient transplacental transfer of antibodies that persisted in infants until at least 6 months post-birth., Conclusion: Consistent with the high titers of transplacentally transferred antibodies, this trial suggests a reduced risk of any/severe MA-RSV-LRTD and RSV hospitalization until 6 months post-birth in infants born to mothers immunized with RSVPreF3-Mat during pregnancy. However, vaccine development was terminated due to an identified preterm birth risk., Trial Registration: ClinicalTrials.gov: NCT04605159., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)