Background Gastrointestinal disorders (GIDs) represent a large public health burden, affecting an estimated 60–70 million Americans annually. Our goal was to examine the relationship between GID and the most common mental health disorders in a national group of newly returning veterans. We also evaluated gender differences in the association of mental health disorders and GID. Methods We utilized a retrospective, longitudinal cohort analysis of veterans’ health records. Participants were 603,221 Iraq and Afghanistan veterans who were new users of VA healthcare from October 7, 2001 (start of the war in Afghanistan) to December 31, 2010. Results The prevalence of GID in newly returning veterans was nearly 20%, and veterans with a mental health disorder were at least twice as likely to have a GID as those without mental health disorders. For women, the increased risk of all GIDs was greatest among those with depression. Among men, the increased risk of irritable bowel syndrome (IBS) was greatest among those with posttraumatic stress disorder. IBS was the GID most strongly associated with mental health conditions among both genders. Conclusions The large proportion of newly returning veterans with GIDs and comorbid mental health diagnoses is concerning. Successful detection and treatment of GIDs associated with mental health disorders will require integrated efforts from primary care and mental health.