OBJECTIVE The cost-effectiveness of passive immunisation against respiratory syncytial virus (RSV) in the Netherlands was studied by assessing incremental costs to prevent one hospitalisation in high-risk children using a novel individualised monthly approach. METHODS Cost-effectiveness analysis was performed by combining estimates of individual hospitalisation costs and monthly hospitalisation risks, with immunisation costs, parental costs and efficacy of passive immunisation for a reference case with the highest hospitalisation risks and costs of hospitalisation during the RSV season (male, gestational age < or =28 weeks, birth weight < or =2500 g, having bronchopulmonary dysplasia (BPD), aged 0 months at the beginning of the season (October)). Various sensitivity analyses and a cost-neutrality analysis were performed. RESULTS Cost-effectiveness of passive immunisation varied widely by child characteristics and seasonal month. For the reference case it was most cost effective in December at euro13,190 per hospitalisation averted. Cost-effectiveness was most sensitive to changes in hospitalisation risk. For the reference case, cost neutrality was reached in December, if acquisition costs of passive immunisation decreased from euro 930 to euro 375, monthly hospitalisation risk increased from 7.6% to 17%, or hospitalisation costs increased from euro 10 250 to euro 23 250 per hospitalisation. Even if passive immunisation prevented all hospitalisations, costs per hospitalisation averted in December would still exceed euro 2645. CONCLUSIONS Although cost-effectiveness of passive immunisation varied strongly by child characteristics and seasonal month, incremental costs per hospitalisation averted were always high. A restrictive immunisation policy only immunising children with BPD in high-risk months is therefore recommended. The costs of passive immunisation would have to be considerably reduced to achieve cost-effectiveness.