The World Health Organization declared smallpox eradicated worldwide in 1980, and no new cases have been reported since then. All countries worldwide discontinued smallpox vaccination by the early 1980s at the latest. The September 11 attacks reignited fears of smallpox being used as a biological weapon, as the virus could have been diverted from one of the two laboratories in the world where it is contained. As part of its plan to combat bioterrorism, the Ministry of Health asked the Institute for Health Surveillance to assess the risk of an epidemic in the event of the virus’s introduction and to propose recommendations regarding potential vaccination strategies to be implemented. A preliminary analysis aimed at assessing the dynamics of the virus’s spread following initial exposure was conducted, based on available data regarding the disease’s transmission modes, its contagiousness, and the French population’s immune profile with respect to smallpox. An analysis of the control strategies implemented internationally during the eradication campaign was also carried out. Finally, an estimate of the frequency and severity of vaccination side effects was conducted. Based on these data, an assessment of the benefit-risk balance for various vaccination scenarios (vaccination/revaccination of the entire French population, all healthcare professionals, or healthcare professionals at highest risk) was performed for different levels of intensity of the terrorist threat. These analyses were presented to the Technical Committee on Vaccinations on October 23, 2001, and served as the basis for the draft opinion submitted by this Committee to the French High Council for Public Health.