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 health care purchaser (National Health Service), which included the cost of administration and hospital care for RSV infections. RESULTS: The use of Palivizumab results in an ICER of £7,042/QALY without discounting, which increases to £16,720/QALY after discounting in the prophylaxis in premature infants and such with BPD. In the prophylaxis in babies with CHD the use of Palivizumab results in an ICER of £2,427/QALY without discounting and £6,664/QALY after discounting. Sensitivity analyses confirmed the robustness of the model. A scenario analysis showed that the inclusion of indirect costs leads to further improvement in the cost-effectiveness outcomes for Palivizumab CONCLUSION: This study showed that Palivizumab is a cost-effective prophylaxis against RSV-infections in infants at high risk: the use of Palivizumab results in positive short and long-term health economic benefits to the health care purchaser.