Objective: Postexposure prophylaxis (PEP) is an important strategy to prevent human immunodeficiency virus acquisition after occupational and nonoccupational exposures. Since exposures to blood and other body fluids commonly occur in a combat setting, it is important to evaluate PEP utilization in the deployed environment. Methods: This is a retrospective review of Public Health, pharmacy, and medical records for PEP cases at a U.S. military trauma hospital in Afghanistan from February 1, 2007 through June 30, 2012. The decision to initiate PEP and the antiretroviral regimens selected were also evaluated for concordance with published Centers for Disease Control (CDC) guidelines. Results: At total of 31 cases were prescribed PEP over the 65-month study period, including 27 occupational and 4 nonoccupational exposures. Of the 23 cases with sufficient data for evaluation, 18 (78.2%) initiated PEP in concordance with CDC guidelines and the discordant cases were prescribed PEP secondary to patient request. Antiretroviral regimens were in concordance with CDC guidelines in 27 of 31 (87.1%) cases, with most discordant cases prescribed differing durations of PEP. Conclusions: Despite the challenges of health care delivery in a deployed environment, the decisions to initiate human immunodeficiency virus PEP and the selection of antiretroviral regimens were typically concordant with CDC guidelines.