Background: Respiratory Syncytial Virus (RSV) is a major health concern, particularly for infants. In France, Nirsevimab, a long-acting monoclonal antibody to prevent RSV-associated lower respiratory tract infections (LRTI) was available from September 2023. We described RSV-associated LRTI hospitalisations during the 2023-2024 season among infants younger than six months born at the Hospices Civils de Lyon (HCL), and evaluated the effectiveness of Nirsevimab against RSV-LRTI hospitalisation. Methods: This observational study included infants born and hospitalised at the HCL during the 2023-2024 season, along with pre-COVID-19 and 2022-2023 seasons. Information on Nirsevimab immunisation status, clinical and perinatal variables were collected through routine care. Infants’ characteristics and incidence risk of hospitalisation per 100 births during 2023-2024 were compared with the historical periods overall and by delay between birth and the onset of the RSV season. Nirsevimab effectiveness was computed by the screening method. Results: During the 2023-2024 season, 83 infants younger than six months were hospitalised with an RSV-associated LRTI. Compared with the historical periods these infants were older. Incidence risk for infants born during the period when immunisation was available were lower than the previous seasons; incidence risk ratios were 0.45 (95% confidence interval (CI): [0.33;0.62]) in 2023-2024 compared with pre-COVID-19 period and 0.53 (95%CI: [0.36;0.77]) compared with 2022-2023 season. Nirsevimab effectiveness was 78.3% (95%CI: [55.9 ;89.5]) with a coverage of 79.3% in the HCL maternities. Conclusions: This study revealed a change in the epidemiology of RSV-associated LRTI hospitalisations in 2023-2024. High coverage and effectiveness were estimated in real-world setting.