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Background and Importance Palivizumab and nirsevimab are monoclonal antibodies for RSV prophylaxis, differing in mechanism, indications, duration, administration, and cost. Nirsevimab provides single-dose seasonal protection, simplifying logistics and increasing coverage.Aim and Objectives To compare hospital consumption and direct pharmaceutical costs of palivizumab and nirsevimab in neonates, assessing economic efficiency. Clinical effectiveness and safety were not evaluated.Material and Methods Retrospective pharmacoeconomic analysis over two RSV seasons. 2023/2024: 46 infants received palivizumab monthly for 5 months; 2024/2025: 292 infants received a single dose of nirsevimab. Drug consumption was measured as vials dispensed. Costs were based on hospital acquisition prices; only drug costs included.Results Total expenditure for palivizumab (2023/2024) was €227,656 (77 vials 0.5 mL + 93 vials 1 mL). Nirsevimab (2024/2025) cost €75,900 (300 vials), representing 33.34% of palivizumab expenditure, a 72.5% reduction, while covering a 534% larger cohort.Conclusion and Relevance Nirsevimab provides substantial budget savings and broader prophylaxis coverage compared with palivizumab. Its single-dose schedule demonstrates greater economic efficiency in the hospital setting, despite the absence of clinical outcome data.Conflict of Interest No conflict of interest