Background Nirsevimab, a novel monoclonal antibody, provides passive immunity against RSV-infections in infants. In October/2023, Spain adopted immunization for children <6 months and those born during the epidemic season. Our main goal was to compare clinical, epidemiological and virological characteristics of respiratory infections in hospitalized infants before and after nirsevimab introduction. Methods. A prospective study was conducted in two Madrid hospitals during the 2022-23 and 2023-24 epidemic seasons. Infants <12 months admitted with lower respiratory tract infections were included. Clinical, epidemiological, and virological characteristics were compared based on admission before or after nirsevimab introduction and whether they received it. Results A total of 717 infants were included: 526 before October/2023 and 191 thereafter. Admissions from October-March 2023/24 decreased by 59% (95%CI:58.7-62.3%) compared to October-March 2022/23. ICU admissions dropped by 74% (95%CI:70.7-77.3%). Of those hospitalized after October/2023, 55(28.8%) received nirsevimab, with 11(20%) contracting RSV. The RSV-detection rate was lower after October/2023 (39% vs. 65%, P<0.001), as was the detection of other respiratory viruses, except rhinovirus and human bocavirus. Patients admitted after October/2023 were older (P=0.002), included fewer infants under 1 month (P=0.005), and had shorter hospital stays (P=0.001). For infants under 3 months, the likelihood of needing a stay > 5 days was 70% lower compared to those admitted before October/2023 (P<0.001;OR:0.39, 95%CI:0.22-0.66). Conclusions Nirsevimab has shown considerable effectiveness in shielding young infants from severe outcomes linked to RSV-infection. Furthermore, our study observed a notable decrease in hospitalizations for infections caused by other respiratory viruses after the introduction of nirsevimab.