In low vaccination coverage regions (LVR) in The Netherlands people often reject participation in the National Immunization Programme for religious reasons. During a rubella epidemic in 2004-2005, 32 pregnant women were notified with rubella, and 11 babies were born with defects related to maternal infection. This study presents a cost-utility analysis of a screening and vaccination programme for rubella focusing on three scenarios: (1) screening non-vaccinated pregnant women in LVR; (2) screening all pregnant women in LVR; (3) screening all non-vaccinated pregnant women in The Netherlands (including pregnant first-generation non-Western immigrant women). Cost-utility was estimated over a 16-year period which included two rubella outbreaks. Observed complications from the 2004-2005 epidemic were used to estimate average cost savings and quality-adjusted life-years (QALY) gained. The programme would be cost-effective (euro1100/QALY gained) when assuming an acceptability of vaccination of 20% in women belonging to orthodox protestant risk groups.