A prospective, observational study of immunizing over 6,000 active-duty troops against smallpox in a 4-week time period was conducted. It focused on the complications of the vaccine and lost workdays. Comparison is made to the complication rates of earlier smallpox immunization programs. In direct response to elevated bioterrorism concerns, the United States military and civilian first-responders have begun a mass smallpox immunization program. This article reviews the experience with implementing such a program in a forward-deployed location while maintaining military readiness. The objectives were to assess the impact of a mass smallpox immunization program on operations in a forward-deployed military setting and to comment on lessons learned in the screening and immunization process. From January 16, 2003 through February 11, 2003 6,002 members of the United States military were immunized in a forward-deployed location. Information was obtained using data from the Air Force Complete Information Tracking Application (AFCITA) and the Global Expeditionary Medical System (GEMS) we plan to calculate the following Main Outcome Measures data: (1)Percentage of individuals eligible to receive the vaccine, (2) Vaccine take rate by CDC criteria, (3) Number of serious complications, (4) Number of life-threatening complications, and (5) Number of manpower days lost as a complication of the vaccine. A total of 6,739 individuals were screened for vaccination with 6,348 (94%) remaining eligible for the vaccine. The “take” rate for the vaccine was 98.6% as per Centers for Disease Control and Prevention (CDC) criteria. The immunization program produced an additional 156 medical visits (2.6% of patients required one visit). A total of 0.55% of immunized individuals lost one or more work days. In conclusion, a mass smallpox vaccination program can be effectively administered in a forward-deployed military setting despite high tempo military operations with minimal operational impact.