OBJECTIVE To investigate the economics of routine antenatal anti-D prophylaxis in the prevention of haemolytic disease of the newborn, in support of the NICE appraisals process. DESIGN Cost effectiveness analysis. SETTING UK NHS. POPULATION/SAMPLE Pregnant women who are RhD-negative. METHODS A model was constructed to estimate the incremental cost effectiveness and cost utility of: (1) offering routine antenatal anti-D prophylaxis to all pregnant women who are RhD-negative; (2) offering routine antenatal anti-D prophylaxis to RhD-negative primigravidae, compared with conventional management alone. Effectiveness estimates were derived from a meta-analysis of two UK community-based studies. Costs were derived from published sources and NHS product lists. Threshold analysis was conducted to reflect the social value of routine antenatal anti-D prophylaxis through incorporating valuations of parental grief and fetal/neonatal loss. MAIN OUTCOME MEASURES Cost per life year gained and cost per quality adjusted life year (QALY) gained. RESULTS The cost per life year gained is in the range pound 5,000- pound 15,000. The inclusion of long term neurodevelopmental problems results in a cost utility ranging between pound 11,000 and pound 52,000 per QALY gained. Threshold analysis suggests that if fetal loss, parental grief and subsequent high intervention pregnancy are valued at greater than 9 QALYs, the comprehensive policy would be more attractive than the primigravidae policy, assuming a maximum acceptable threshold of pound 30,000 per QALY. CONCLUSION Routine antenatal anti-D prophylaxis provides a cost effective intervention for preventing haemolytic disease of the newborn in the pregnancies of women who are RhD-negative.