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Background Increasing international travel places larger populations at risk for infections outside of their usual exposure. Deployed military personnel have unique risks for such infections. Our cohort's rates of travelers' diarrhea and influenza-like illness have been defined, but the rate of travelers with symptoms apart from a clinical syndrome has not. We present a survey of intra-travel symptoms of all travelers and confirmed diagnoses of ill-returned travelers in a cohort of military and civilian travelers. Methods TravMil is a prospective, multicenter observational study enrolling US military beneficiaries traveling outside the continental United States from 2010–2018; beneficiaries could also enroll after travel if they presented for a possible travel-related illness. Demographic information, intra-travel symptoms, and confirmed diagnoses were recorded. Results 2671 travelers embarked on 3050 trips: 63.1% male; median age 38 years (IQR 27, 57); median trip duration 20 days (IQR 13, 46). Common purposes of travel: military deployment (45.9%), vacation (23.7%), and visiting friends/relatives (10.9%). Ninety-seven travelers (3.2%) enrolled post-travel. Top regions of travel: Africa (31.5%), South and Central America/Caribbean (25.5%), and Southeast and North Asia/Oceania (19.4%). During travel, 56.6% experienced gastrointestinal (GI) symptoms, 11.9% respiratory symptoms, and 3.0% fever; of those, 10.3% sought medical care. Eighty returned travelers sought medical care (21 prospective enrollees vs. 59 post-travel enrollees): 5 vs. 17 malaria cases, 3 vs. 16 arbovirus infections, and 6 vs. 14 GI syndromes. All malaria cases in prospective enrollees were in military subjects. Post-travel enrollees accounted for 1 acute human immunodeficiency virus and 3 rickettsial infections. Conclusion A majority of our travelers experienced symptoms during travel. Post-travel diagnoses, although uncommon, emphasize needed improvements in the application of known risk mitigation strategies. Our findings can help clinicians optimize their pretravel counseling by focusing education on self-treatment of common travel-related symptoms, prevention of GI, arthropod-borne, and respiratory illness, and emphasizing symptoms that should prompt medical care. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]