Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV bronchiolitis requiring admission. In 2023-2024, Catalonia and Andorra adopted immunization strategies for children <6 months and those born during the epidemic season. This study evaluates the effectiveness of nirsevimab in preventing hospitalizations from RSV bronchiolitis. In the epidemic season of 2023-2024, a test-negative case-control study was conducted in three hospitals from Catalonia and Andorra. Patients <12 months old admitted with bronchiolitis and tested for RSV using molecular microbiology tests were included. The effectiveness in preventing RSV bronchiolitis hospitalization and severe disease was estimated using multivariate models. Comparisons between immunized, non-immunized, and non-eligible patients were made in prospectively collected epidemiological, clinical, and microbiological variables. Two hundred thirty-four patients were included. RSV was detected in 141/234 (60.2%), being less common in the immunized group (37% vs 75%, p < .001). The rate of immunized patients among those eligible was 59.7%. The estimated effectiveness for RSV-associated lower respiratory tract infection was 81.0% (95% confidence interval: 60.9-90.7), and for preventing severe disease (the need for NIV/CMV), 85.6% (41.7-96.4%). No significant differences by immunization status were observed in patients with RSV concerning viral coinfections, the need for NIV/CMV or length of hospital stay. This study provides real-world evidence of the effectiveness of nirsevimab in preventing RSV-lower respiratory tract infection hospitalization and severe disease in infants during their first RSV season following a systematic immunization program. Immunized patients did not exhibit a higher rate of viral coinfections nor differences in clinical severity once admitted.