Coxiella burnetii is a category B bioterrorism agent. We numerically evaluated the risks and benefits from postexposure prophylaxis (PEP) after an intentional release of C. burnetii to the general population, pregnant women, and other high-risk populations. For each group, we constructed a decision tree to estimate illness and deaths averted by use of PEP/100,000 population. We calculated the threshold points at which the number of PEP-related adverse events was equal to the cases averted. PEP was defined as doxycycline (100 mg 2x/day for 5 days), except for pregnant women, where we assumed a PEP of trimethoprim-sulfamethoxazole (160 mg/800 mg 2x/day) for the duration of the pregnancy. PEP would begin 8-12 days postexposure. On the basis of upper-bound probability estimates of PEP-related adverse events for doxycycline, we concluded that the risk for Q fever illness outweighs the risk for antimicrobial drug-related adverse events when the probability of C. burnetii exposure is >or=7% (pregnant women using trimethoprim-sulfamethoxazole = 16%).