Significant perinatal distress and depression affects 14% of women, producing short and long term consequences for the family. This suggests that measures for early detection are important, and non-identification of these women may exacerbate difficulties. Screening provides an opportunity to access large numbers of women and facilitate pathways to best-practice care. A valid, reliable, economical screening tool (the Edinburgh Postnatal Depression Scale, EPDS) is available. Arguments against screening pertain largely to lack of evidence about the acceptability of routine use of the EPDS during pregnancy and the postnatal period, and inadequate evidence regarding outcomes and cost-effectiveness. To address these concerns, the National Postnatal Depression Prevention and Early Intervention Program will evaluate outcomes of screening in terms of acceptability, cost-effectiveness, access and satisfaction with management in up to 100 000 women.