Objective: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from maternal platelet-directed antibodies which can cause severe intracranial haemorrhage (ICH) in fetuses and new-borns. Screening for human platelet antigen-1a (HPA-1a) directed antibodies during pregnancy could allow for timely intervention with antenatal treatment and prevent the occurrence of ICH. We aim to assess the cost-effectiveness of adding screening for anti-HPA-1a to the prenatal screening program. Design: A decision analysis model was developed. Setting: The Netherlands. Population: 171,713 pregnant women. Methods: Lifetime costs and effects of antenatal anti-HPA-1a screening with subsequent diagnostic and treatment interventions were compared to the current situation without screening in the Netherlands. Model parameters were based on literature and expert opinions. One-way-sensitivity analysis and probabilistic sensitivity analysis were performed. Main Outcome Measures: Incremental cost-effectiveness ratio (ICER). Results: Adding screening for HPA-1a antibodies to the current antenatal screening program of the Netherlands will lead to an additional cost of 4.7 million euro and a gain of 226 Quality-Adjusted Life Years (QALY) per year, indicating an ICER of \euro20,782 per QALY gained. One-way sensitivity analysis showed that the uncertainty around the incidence of ICH, lifetime costs of disabled children and the probability of having antibody quantitation >3.0 IU/ml at 20 weeks had the highest effect on the ICER. Conclusion: Antenatal HPA-1a screening might be cost-effective. To obtain more knowledge and thereby reduce the uncertainty on risk stratification, a pilot screening program is warranted. Funding: Sanquin