Introduction: Over the past 15 years, members of the U.S Armed Forces have experienced higher rates and duration of deployments to malaria endemic areas in Central Asia. Doxycycline remains the preferred form of chemoprophylaxis for troops deployed to this region. Although the propensity of doxycycline to cause esophageal injury is well known and preventable, it continues to account for one of the most substantial gastrointestinal co-morbidities of our ongoing presence overseas. Methods: This case series retrospectively examines 5 cases of doxycycline-induced esophageal ulcers that presented to a Role III Combat Hospital in Afghanistan during a 2 month span between February and April 2016. Data reviewed includes demographics, comorbidities, presenting symptoms, endoscopic characteristics, exacerbating factors, and outcomes. Results: Our study includes 5 patients between the ages of 25-44, one of which was female. There was no history of gastrointestinal or systemic disease. Odynophagia was the presenting symptom in four patients, and substernal chest pressure in one. Mean duration of symptoms prior to presentation was 6.8 days (range 2-12 days). Two of the five patients reported weight loss (5-7 lbs) due to odynophagia. On endoscopy, two patients had 1-2cm classic kissing ulcers. The remaining cases had severe ulceration with >80% circumferential distribution. All lesions were noted between 21-33 cm from the incisors. All patients endorsed taking doxycycline with < 6 oz. of fluid and three out of five reported taking doxycycline prior to bedtime. No standardized counseling was reported for medication administration or side effects. No other risk factors for esophageal ulceration were found in any case. All patients received supportive therapy and were returned to duty on atovaquone/proguanil as alternate prophylaxis. Discussion The use of doxycycline as anti-malarial prophylaxis and its associated risk of esophageal injury presents a unique challenge in the deployed setting. Thousands of healthy service members are taking this medication daily, with evidence of poor administration precautions and late presentations in the course of injury. This is complicated by lack of standardized counseling, suboptimal alternatives to doxycycline, and limited availability of diagnostic endoscopy. Given the anticipated need for our continued U.S. military presence in the region, these root causes must be addressed to reduce the disease burden on our troops and mission.Figure 1Figure 2Figure 3