Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection (LRTI) hospitalisations in infants. Madeira was the first Portuguese region to recommend immunoprophylaxis with nirsevimab, an anti-RSV monoclonal antibody, for all infants in their first RSV season. The immunisation campaign, from November 2023 to March 2024, targeted infants born during the campaign (seasonal group), and those born between April and October, 2023 (catch-up group). This study aimed to assess nirsevimab effectiveness in preventing RSV-related LRTI hospitalisations. Methods: A population-based longitudinal observational study was conducted. Follow-up lasted until 150 days post-immunisation, campaign end (non-recipients), hospitalisation, or death, whichever occurred first. Nirsevimab effectiveness was estimated using an adjusted Cox proportional hazards model. The number needed to immunise (NNI) was calculated from absolute risk reduction. Averted cases were estimated from historical data, excluding the COVID-19 pandemic period. Results: The overall immunisation rate was 97.4% (1710/1756): similar in the seasonal (97.7%, 728/745) and catch-up (97.1%, 982/1011) groups. RSV-related LRTI hospitalisations occurred in 0.4% (6/1710) of nirsevimab recipients versus 4.3% (2/46) of non-recipients, with an estimated effectiveness of 94.6% (95% CI 72.6-98.9). NNI was 25. Supplemental oxygen therapy duration decreased significantly compared to previous seasons ( P=.039). Number of averted cases was 45 (IQR 15-83), with a 79.6% reduction in hospitalisations (IQR 62.6-90.9). Conclusion: Nirsevimab was effective in reducing RSV-related LRTI hospitalisations in a real-world setting, offering useful evidence for future RSV immunisation strategies.