Background: The healthcare and socio-economic burden resulting from influenza A (H1N1) pdm09 in Spain was considerable. Our aim was to estimate and compare the management (resource utilization) and economic healthcare impact in an at-risk group of unvaccinated pregnant women with an unvaccinated group of non-pregnant woman of childbearing age (15-44 yr old). Methods: We addressed this question with a longitudinal, observational, multicentre study. Inputs were the requirements in managing both groups of women. Outcome measures were healthcare costs. Direct healthcare (including medical utilisation, prescriptions of antivirals, medication, diagnostic tests, and hospitalisation) costs and indirect (productivity loss) costs were considered. Unit of cost was attributed to the frequency of health service resources utilisation. The mean cost per patient was calculated in this group of women. Results: We found that the influenza clinical pattern was worse in non-pregnant women as they had a high medical risk of 20.4% versus 6.1% of pregnant women. Non-pregnant required more antipyretics and antibiotics, and needed more health service resource utilisation (338 medical visits in non-pregnant women vs. 42 in pregnant women). The total cost of non-pregnant women was higher (€4,689.4/non-pregnant and €2,945.07/pregnant). Conclusions: Cost per (H1N1) pdm09 was lower for pregnant women, probably due to more preventive measures adopted for their protection in Spain. The highest costs were incurred by hospitalisations/day and work absenteeism for non-pregnant than for pregnant women. These data will allow better future pandemic influenza planning.