OBJECTIVES: Respiratory syncytial virus (RSV) infection is one of the major causes of respiratory symptoms in infants in many countries, infecting virtually every child by the age of two. Currently, several Phase 1 trials with RSV vaccines in infants are running or have been completed. Although no efficacy estimates are yet available, cost-effectiveness estimates might be informative enabling preliminary positioning. METHODS: A decision analysis model was developed following a Dutch birth cohort for 12 months. Vaccination strategies that were reviewed included vaccination at specific ages, different dosing schemes and seasonal versus year round vaccination. The impact of the assumptions was explored in sensitivity analyses. Outcome measures included number of GP visits, hospitalizations and deaths, costs, quality-adjusted life years and ICERs. RESULTS: Without vaccination, an annual number of 28,738 of RSV-related GP visits, 1,623 hospitalizations, and 4.5 deaths are estimated in the 0-1 year olds. The total cost to society in the non-vaccination scenario was €7.7 million and the annual disease burden was estimated at 597 QALYs. In case all infants would be offered a 3-dose RSV vaccination scheme at 0/1/3 months of age, the total annual net costs were estimated to increase to €21.2 million but a significant number of hospitalizations and deaths could be averted, 544 and 1.5 respectively. The ICER was estimated € 34,142 (95%CI: € 21,652 - € 87,766) per QALY. A reduced dose schedule, seasonal vaccination, out-of pocket payments all resulted in a more favorable ICERs while lowering the expected vaccine efficacy or delaying the time of vaccination in less favorable ICERs. CONCLUSIONS: Recent updates on burden of disease estimates were used and utilities included but due to the absence of trial data still a number of assumptions were used. The outcomes of this modeling exercise show that a vaccine against RSV might be cost-effective, but trial data are warranted.