OBJECTIVES: To assess the cost-effectiveness of Palivizumab, a prevention against respiratory syncytial virus (RSV) infections in infants at high risk, such as premature babies, infants with bronchopulmonary dysplasia (BPD), and children with congenital heart disease (CHD). METHODS: A decision tree model was used to estimate the cost-effectiveness of Palivizumab in high-risk children. The data sources included published literature, the Palivizumab clinical trials, official price/tariff lists and national population statistics. The primary perspective of the study was that of the society, which included cost of the complications asthma and wheezing. RESULTS: The use of Palivizumab results in an ICER of € 12,728/QALY without discounting for effectiveness, which increases to € 20,236/QALY after discounting for effectiveness in the prematurity/BPD indications. In the CHD indication the use of Palivizumab results in an ICER of € 4,256/QALY without discounting for effectiveness and € 7,067/QALY after discounting for effectiveness. Sensitivity analyses confirmed the robustness of the model. CONCLUSION: This study showed that Palivizumab is a cost-effective treatment against RSV in infants at high risk: the use of Palivizumab results in positive short and long-term health economic benefits to the society and health authorities.