Abstract: INTRODUCTION: Irritable bowel syndrome (IBS) is a chronic gastrointestinal pain condition that has not been thoroughly studied in relation to environmental exposures and other health issues. Veterans are more susceptible to IBS and may experience specific service-related risks for developing the condition. Evaluating the prevalence of IBS and its links to military service, environmental factors, and health conditions in both men and women Veterans could improve our understanding of etiological factors contributing to IBS. METHODS: This observational cohort study, using a large-scale epidemiological sample from the Million Veteran Program, included self-report data from 546,246 Veterans and examined the prevalence of IBS and its association with military service history, environmental exposures, and health comorbidities. RESULTS: Of the 546,246 Veterans included, 497,287 (91.0%) were men, and 48,959 (9.0%) were women. The prevalence of IBS was higher in women (13.8%) than in men (4.2%) and varied by race and ethnicity, with the highest in White women (14.7%). Veterans with IBS had worse general health, more pain, and greater pain interference. We found associations between IBS and aspects of military service, including service post-September 2001, and environmental exposures, including a history of exposure to chemical and biological warfare and anti-nerve agent pills. Individuals with IBS were at a greater likelihood of digestive, neurological, and psychiatric conditions and greater opioid use. DISCUSSION: IBS prevalence varied across sex, race, and environmental exposures. IBS was associated with several domains of health conditions, including gastrointestinal, psychiatric, and neurological. Our results highlight the link between IBS and environmental factors, including toxicants, and encourage future research into the mechanisms underlying this association.