Background. Influenza vaccination of health care workers has been recommended since 1984. Multiple strategies to enhance vaccination rates have been suggested, but national rates have remained low. Methods. BJC HealthCare is a large Midwestern health care organization with ̃26,000 employees. Because organizational vaccination rates remained below target levels, influenza vaccination was made a condition of employment for all employees in 2008. Medical or religious exemptions could be requested. Predetermined medical contraindications include hypersensitivity to eggs, prior hypersensitivity reaction to influenza vaccine, and history of Guillan-Barré syndrome. Medical exemption requests were reviewed by occupational health nurses and their medical directors. Employees who were neither vaccinated nor exempted by 15 December 2008 were not scheduled for work. Employees still not vaccinated or exempt by 15 January 2009 were terminated. Results. Overall, 25,561 (98.4%) of 25,980 active employees were vaccinated. Ninety employees (0.3%) received religious exemptions, and 321 (1.2%) received medical exemptions. Eight employees (0.03%) were not vaccinated or exempted. Reasons for medical exemption included allergy to eggs (107 [33%] ), prior allergic reaction or allergy to other vaccine component (83 [26%]), history of Guillan-Barré syndrome (15 [5%]), and other (116 [36%]), including 14 because of pregnancy. Many requests reflected misinformation about the vaccine. Conclusions. A mandatory influenza vaccination campaign successfully increased vaccination rates. Fewer employees sought medical or religious exemptions than had signed declination statements during the previous year. A standardized medical exemption request form would simplify the request and review process for employees, their physicians, and occupational health and will be used next year.