Background: Infectious diseases are a leading cause of morbidity among travelers to resource-limited regions and primary prevention is a cornerstone to risk reduction. Chemoprophylaxis has been successfully utilized for specific diseases. Methods: We assessed self-reported compliance to daily chemoprophylaxis among deployed US military personnel. A 21 item self-completed questionnaire was completed by military personnel during mid-deployment. Results: The perception of high disease risk was associated with an increased likelihood of compliance with daily chemoprophylaxis. However, 60 % of respondents stated they would not comply with a daily regimen. Conclusions: These data highlight the complexity of perceived risk and the difficulties with prophylactic interventions.