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Objective: To estimate the costs and effects of different treatment strategies with intrapartum antibiotic prophylaxis to prevent early-onset group B streptococcal (GBS) disease in the Netherlands. The treatment strategies include a risk-based strategy, a screening-based strategy, a combined screening/risk-based strategy and the current Dutch guideline. Design: Cost-effectiveness analysis based on decision model. Setting Obstetric care system in the Netherlands. Population/Sample Hypothetical cohort of 200,000 neonates. Methods: A decision analysis model was used to compare the costs and effects of different treatment strategies with no treatment. Baseline estimates were derived from literature and a survey among parents of children affected by GBS disease. The analysis was performed from a societal perspective, and costs and effects were discounted at a percentage of 3%. Main outcome measures Cost per quality adjusted of life-year (QALY). Result The risk-based strategy will prevent 352 cases of early-onset GBS for € 5.0 million, indicating a cost-effectiveness ratio of € 7600 per QALY gained. The combined screening risk-based strategy has comparable results. The current Dutch guideline resulted in lower effects for higher costs. The screening-based strategy shows the highest reduction in cases of early-onset GBS, however, at a cost-effectiveness ratio of € 59,300 per QALY gained. Introducing the polymerase chain reaction (PCR) test may lead to a more favourable cost-effectiveness ratio. Conclusion: In the Dutch system, the combined screening/risk-based strategy and the risk-based strategy have reasonable cost-effectiveness ratios. If it becomes feasible to add the PCR test, the cost-effectiveness of the combined screening/risk-based strategy may even be more favourable. © RCOG 2005.