BackgroundVeterans of the 1990–1991 Gulf War have experienced excess health problems, most prominently the multisymptom condition Gulf War illness (GWI). The Department of Veterans Affairs (VA) Cooperative Studies Program #2006 “Genomics of Gulf War Illness in Veterans” project was established to address important questions concerning pathobiological and genetic aspects of GWI. The current study evaluated patterns of chronic ill health/GWI in the VA Million Veteran Program (MVP) Gulf War veteran cohort in relation to wartime exposures and key features of deployment, 27–30 years after Gulf War service.MethodsMVP participants who served in the 1990–1991 Gulf War completed the MVP Gulf War Era Survey in 2018–2020. Survey responses provided detailed information on veterans’ health, Gulf War exposures, and deployment time periods and locations. Analyses determined associations of three defined GWI/ill health outcomes with Gulf War deployment characteristics and exposures.ResultsThe final cohort included 14,103 veterans; demographic and military characteristics of the sample were similar to the full population of U.S. 1990–1991 Gulf War veterans. Overall, a substantial number of veterans experienced chronic ill health, as indicated by three defined outcomes: 49% reported their health as fair or poor, 31% met Centers for Disease Control and Prevention criteria for severe GWI, and 20% had been diagnosed with GWI by a healthcare provider. Health outcomes varied consistently with veterans’ demographic and military characteristics, and with exposures during deployment. All outcomes were most prevalent among youngest veterans (< 50 years), Army and Marine Corps veterans, enlisted personnel (vs. officers), veterans located in Iraq and/or Kuwait for at least 7 days, and veterans who remained in theater from January/February 1991 through the summer of 1991. In multivariable models, GWI/ill health was most strongly associated with three exposures: chemical/biological warfare agents, taking pyridostigmine bromide pills, and use of skin pesticides.ConclusionsResults from this large cohort indicate that GWI/chronic ill health continues to affect a large proportion of Gulf War veterans in patterns associated with 1990-1991 Gulf War deployment and exposures. Findings establish a foundation for comprehensive evaluation of genetic factors and deployment exposures in relation to GWI risk and pathobiology.