OBJECTIVES: Respiratory Syncytial Virus (RSV) is a seasonal virus, playing a dominant role in infants severe lower respiratory tract infections. In the absence of vaccine, Palivizumab is the only approved prophylactic treatment for the prevention of severe RSV disease. The purpose of this study was to evaluate the net budget impact of Palivizumab versus no prophylaxis in high-risk infants in Algeria. METHODS: A simple and transparent decisional tree for the first year of life (acute disease), as well as a Markov chain for the subsequent nineteen years of life (sequelae) were build up for each of the four sub-population groups (Preterm, Moderate BPD, Severe BPD, and CHD) as defined by the national recommendations for use of Palivizumab. Model inputs were derived from clinical and real-world evidence, public data, and published literature. Costs of doctor visits, hospitalizations, heart surgery delaying, nosocomial infections, sequelae, and parent work absence were included. Over the 20-year time horizon, the two scenarios were compared to estimate the Palivizumab net budget impact for the 2020-2024 period. Costs were discounted at 3.5% rate. One way sensitivity analysis was conducted to assess impact of different model parameters on the outputs. RESULTS: The national recommendations eligible population represents only 7% of the overall population corresponding to Palivizumab approved indications in Algeria. For an average annual treatment cost of DZD 1.015 billion, the prophylaxis generates DZD 5.833 billion savings over the 2020-2024 period. Palivizumab-associated savings surpass the treatment cost, with net budget impact estimated to DZD -760 million over 2020-2024 period. It also reduces the healthcare resources utilization by 22,488 days in hospital ward, and 10,010 days in intensive care during the same period. CONCLUSIONS: This study has shown that Palivizumab prophylaxis is a cost-saving alternative for the prevention of severe RSV infections in high-risk eligible infants, as defined by the national recommendations in Algeria.