Objectives To assess the cost effectiveness of palivizumab prophylaxis used to prevent RSV hospitalization (RSVH) in high-risk infants in the Dutch healthcare setting. Methods A decision tree model was used to estimate the cost-effectiveness of palivizumab prophylaxis in high-risk infants in The Netherlands. Data sources included published literature, the palivizumab pivotal trials, official price/tariff lists and national population statistics. In the analysis the positive impact of RSV prevention on long-term outcomes was considered. The study was conducted from the perspective of society (primary analysis) and the healthcare purchaser (secondary analysis). Results The use of palivizumab results in undiscounted incremental cost effectiveness ratios of ?12,728 per quality-adjusted life-year (QALY) and ?4,256/QALY in the in preterm/bronchopulmonary dysplasia (BPD) and congenital heart disease (CHD) indications, respectively. Inclusion of indirect costs leads to even more favourable cost-effectiveness outcomes. Conclusion Palivizumab provides cost-effective prophylaxis against RSV in high-risk infants. The use of palivizumab in these children results in positive short- and long-term health economic benefits. Funded by Abbott.