Risk groups with increased vulnerability for influenza complications such as pregnant women, persons with underlying illnesses as well as persons who come into contact with them, such as health care workers, are currently given priority (along with other classic target groups) to receive seasonal influenza vaccination in Belgium. We aimed to evaluate this policy from a health care payer perspective by cost-effectiveness analysis in the three specific target groups above, while accounting for effects beyond the target group. Increasing the coverage of influenza vaccination is likely to be cost-effective for pregnant women (median (sic)6589 per quality-adjusted life-year (QALY) gained [(sic)4073-(sic)10,249]) and health care workers (median (sic)24,096/QALY gained [(sic)16,442-(sic)36,342]), if this can be achieved without incurring additional administration costs. Assuming an additional physician's consult is charged to administer each additional vaccine dose, the cost-effectiveness of vaccinating pregnant women depends strongly on the extent of its impact on the neonate's health. For health care workers, the assumed number of preventable secondary infections has a strong influence on the cost-effectiveness. Vaccinating people with underlying illnesses is likely highly cost-effective above 50 years of age and borderline cost-effective for younger persons, depending on relative life expectancy and vaccine efficacy in this risk group compared to the general population. The case-fatality ratios of the target group, of the secondary affected groups and vaccine efficacy are key sources of uncertainty. (C) 2014 Elsevier Ltd. All rights reserved. ; This study was commissioned and co-financed by the Health Care Knowledge Centre (KCE) of the Belgian Federal government. Adriaan Blommaert acknowledges support from the University of Antwerp concerted research action number 23405 (BOE-GOA); Joke Bilcke is supported by a postdoctoral grant from the Research Foundation Flanders (FWO); Yannick Vandendijck is supported by a ...