OBJECTIVES: To determine the cost-effectiveness of palivizumab for the prevention of serious lower respiratory tract infection requiring hospitalization caused by RSV compared to no prophylaxis in high-risk infants born at 33-35 weeks of gestational age (wGA) according to the Dutch RISK model. METHODS: A decision tree model was developed using data from published literature, palivizumab clinical trials, the Dutch RISK score model, official price/tariff lists and Dutch national population statistic. The comparator was no prophylaxis.  The primary perspective of the study was that of the society in The Netherlands.  Time horizon was lifetime.  The cost valuation is based on the direct healthcare costs, direct nonmedical costs and indirect costs.  Costs were assessed in 2012 Euros.  The costs and utilities are discounted by 4% and 1.5%, respectively, from the second year onwards, and no discounting is applied in the first year. RESULTS: The base case results show that the use of palivizumab leads to an additional cost of € 4,116, whereas the use of palivizumab leads to a gain of 0.201 life years and 0.265 QALYs. Although the use of palivizumab increases the costs compared with no prophylaxis, palivizumab-treated patients experienced more QALYs and a gain in life years. Subsequently, palivizumab results in an ICER of € 15,520 per QALY gained compared to no prophylaxis. The ICER in cost per LYG is € 20,440. CONCLUSIONS: This analysis showed that palivizumab was cost-effective as a prophylaxis against RSV infection requiring hospitalisation in high-risk late premature infants compared to no prophylaxis. Extensive sensitivity analyses and explored scenarios underline the robustness of the demonstrated base case cost-effectiveness.