To inform policy and decision makers, a cost-effectiveness model was developed to predict the costeffectiveness of implementing two hypothetical management strategies separately and concurrently on the mitigation of deployment-associated travelers' diarrhea (TD) burden. The first management strategy aimed to increase the likelihood that a deployed service member with TD will seek medical care earlier in the disease course compared with current patterns; the second strategy aimed to optimize provider treatment practices through the implementation of a Department of Defense Clinical Practice Guideline. Outcome measures selected to compare management strategies were duty days lost averted (DDL-averted) and a cost effectiveness ratio (CER) of cost per DDL-averted (USD/DDL-averted). Increasing health care and by seeking it more often and earlier in the disease course as a stand-alone management strategy produced more DDL (worse) than the base case (up to 8,898 DDL-gained per year) at an increased cost to the Department of Defense (CER $193). Increasing provider use of an optimal evidence-based treatment algorithm through Clinical Practice Guidelines prevented 5,299 DDL per year with overall cost savings (CER -$74). A combination of both strategies produced the greatest gain in DDL-averted (6,887) with a modest cost increase (CER $118). The application of this model demonstrates that changes in TD management during deployment can be implemented to reduce DDL with likely favorable impacts on mission capability and individual health readiness. The hypothetical combination strategy evaluated prevents the most DDL compared with current practice and is associated with a modest cost increase.