In response to Section 510 of the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxins (PACT) Act of 2022, the U.S. Department of Veterans Affairs (VA) conducted a fit-for-purpose systematic literature review to assess the potential acute and long-term health effects of jet fuels used by the Armed Forces. Jet fuels are common exposures among military personnel with reported, but incompletely characterized impacts on human health. Previous literature summarized acute health outcomes associated with exposure to jet fuels, including hematological and neurological effects; however, there is limited information on long-term health outcomes. VA adapted the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) methodology to identify health hazards (i.e., potential health outcomes) related to exposure to jet fuel by applying the following six steps in its systematic review: 1) defining the Population, Exposure, Comparator, and Outcome (PECO) statement; 2) conducting a systematic literature search; 3) screening relevant texts; 4) evaluating study quality across multiple domains, including types of health outcomes; 5) extracting data from the literature; and 6) evidence synthesis. The systematic literature search conducted through January 10, 2023, yielded 3,280 unique references, with most of these eliminated after review of the abstract. After full text review of 285 potentially relevant studies, 69 met eligibility criteria, with 28 unique primary epidemiological studies (described in 36 references), 19 reviews, and 14 case reports/series. The 28 primary studies reported on a range of health outcomes across 14 organ systems. Most studies reported on nervous system outcomes (n = 13), cancers (n = 8), or respiratory system outcomes (n = 7). Of the 28 included studies, eight were rated as medium confidence for at least one health outcome; 17 were rated as low confidence; and six were considered uninformative. Health outcomes related to the nervous system were evaluated in four medium confidence studies, with cancers and outcomes related to the immune system, mental health, the female reproductive system, and the respiratory system being evaluated in one medium confidence study each. Overall, the review found slight evidence of associations between jet fuel exposure and effects on the nervous system, mental health, and the respiratory system, as well as the development of kidney and bladder cancers. There is indeterminate evidence for all other health outcomes represented in the published literature. The adaptation of the IRIS framework allowed VA to consistently describe the availability and quality of epidemiological evidence supporting conclusions about jet fuel exposure and acute or long-term health outcomes. This approach will be used in future evaluations of the potential long-term implications of military environmental exposures as a part of VA’s new presumption decision-making process. Utilizing well-established scientific research frameworks in reports to policymakers promotes transparency and emphasizes objectivity, and ultimately, helps VA honor its commitments to the Veterans who served our nation .