Background: Acute diarrheal illness during deployment causes significant morbidity and loss of duty days. Effective and timely treatment is needed to reduce individual, unit, and health system performance impacts. Methods: This critical appraisal of the literature, as part of the development of expert consensus guidelines, asked several key questions related to self-care and healthcare-seeking behavior, antibiotics for self-treatment of travelers’ diarrhea, what antibiotics/regimens should be considered for treatment of acute watery diarrhea and febrile diarrhea and/or dysentery, and when and what laboratory diagnostics should be used to support management of deploymentrelated travelers’ diarrhea. Studies of acute diarrhea management in military and other travelers were assessed for relevance and quality. On the basis of this critical appraisal, guideline recommendations were developed and graded by the Expert Panel using good standards in clinical guideline development methodology. Results: New definitions for defining the severity of diarrhea during deployment were established. A total of 13 graded recommendations on the topics of prophylaxis, therapy and diagnosis, and follow-up were developed. In addition, four non-graded consensus-based statements were adopted. Conclusions: Successful management of acute diarrheal illness during deployment requires action at the provider, population, and commander levels. Strong evidence supports that single-dose antimicrobial therapy is effective in most cases of moderate to severe acute diarrheal illness during deployment. Further studies are needed to address gaps in available knowledge regarding optimal therapies for treatment, prevention, and laboratory testing of acute diarrheal illness.