- Background The population at risk of adverse events after smallpox vaccination has increased in recent years. This has important implications for preparedness strategies against bioterrorism with the variola virus. The aim of the study was to estimate the size of this special population in Israel. Methods The study was conducted in January 2010. Data on patients with contraindications to smallpox vaccination, as delineated by the Israel Ministry of Health for planning post-event strategies, were retrieved from the computerized records of the Department of AIDS and Tuberculosis and the Transplantation Center of the Israel Ministry of Health. In addition, the database of the main Health Maintenance Organization in Israel which insures 60% of the national population was searched using ICD-9 codes and specific medications issued in the last quarter of 2009. Results Of the 7,563,800 persons residing in Israel in January 2010, 326,318 were at risk of an adverse event after smallpox vaccination. Conclusion Approximately 4.3% of the Israeli population should not be exposed to the currently used smallpox vaccine. This knowledge is important to ensure the effectiveness of mass vaccination programs in the event of a bioterror attack.