Background. Intentional exposures to aerosolized Bacillus anthracis spores have caused fatalities. Objective. To evaluate the cost-effectiveness of strategies to reduce mortality from future inhalational anthrax exposures. Methods. Computer cohort simulation of a 100,000-person single-site exposure (worst-case scenario) and a 100-person multiplesite exposure (resembling the recent US attack). For each scenario, universal vaccination and an emergency surveillance and response (ESR) system were compared with a default strategy that assumed eventual discovery of the exposure. Results. If an exposure was unlikely to occur or was small in scale, neither vaccination nor an ESR system was cost-effective. If an exposure was certain and large in scale, an ESR system was more cost-effective than vaccination ($73 v. $29,600 per life-year saved), and a rapid response saved more lives than improved surveillance. Conclusions. Strategies to reduce deaths from anthrax attacks are cost-effective only if large exposures are certain. A faster response is more beneficial than enhanced surveillance