OBJECTIVES: Childhood prevention programs are important and imperative public health initiatives.  However, prevention programs are often associated with considerable investments. This budget impact analysis was undertaken to position the Italian investment for a program to prevent respiratory syncytial virus (RSV) consequences in high-risk infants  using palivizumab. This prevention program is compared to an existing immunization program in the Lombardy region of Italy: Human Papillomavirus Vaccine [Types 6, 11, 16, 18] (HPV), considered standard of care. METHODS: Two budget impact models were developed to assess the impact of two different programs on Regional Health Service (RHS) expenditure: the budget impact of RSV prophylaxis program was compared with a non-prophylaxis program, while the budget impact of HPV active prophylaxis was compared with a non-prophylaxis approach. Only direct costs based on disease prevalence, and program efficacy were included. The model includes RSV prophylaxis administration costs, RSV-related resource consumption (visits, long term sequelae) and RSV hospitalization over one year; for HPV prevention program, one year prophylaxis was assessed against 5 years disease costs due to the low incidence of HPV related disease in 1 year. Eligible subjects were preterm and high-risk infants (as established by national guidelines) for RVS program and all 12-year-old girls cohort for HPV program. RESULTS: RSV prophylaxis expenditure was estimated at €11,577,776 in the  prophylaxis program arm versus €5,206,534 in the ‘without prophylaxis program’ arm, while for HPV prevention program, vaccination program expenditure (including vaccine cost) would be 13,068,025€ vs. 356,385€ in no-vaccine arm. The net budgetary impact was calculated at €6.4 million for RSV vs. €12.7 million for HPV vaccination. CONCLUSIONS: Considering the RHS perspective, the budget impact of palivizumab had lower program costs and higher disease cost offsets vs. HPV vaccination program, positioning its economic value well within the parameters of cost-effective childhood prevention programs