Abstract: Objective: . To evaluate the impact of respiratory syncytial virus (RSV) prophylaxis with nirsevimab during its 2nd year of administration and analyze the differences between the different strategies implemented across Spanish autonomous communities (ACs) during the current epidemic season. Methods: We conducted a retrospective analytical study with 15 pediatric emergency departments across 9 ACs. We included all infants younger than 6 months who were treated in November, December, and January during 5 epidemic seasons (2018-2019, 2019-2020, 2022-2023, 2023-2024, and 2024-2025). Results: Compared with the average of epidemic seasons prior to the introduction of nirsevimab, in 2024-2025 there was a 65.5% decrease in episodes of acute bronchiolitis (95% CI, 64.3-63.7; P .001). Hospital admissions for bronchiolitis decreased by 74.7% (95% CI, 72.7-76.6; P .001), and PICU admissions fell by 72.9% (95% CI, 68.1-77.2; P .001). The reductions achieved in the 2024-2025 season were greater than those observed in the 2023-2024 season. The hospital from the AC that decided not to immunize infants born before the start of the epidemic had the worst outcomes. Among the ACs that applied the same strategy, worse outcomes were observed in the one that immunized out-of-season infants through selected hospitals rather than primary care centers.

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