Background and Purpose: Military personnel commonly report potential exposure to jet fuels; however, the effects on human health are incompletely characterized. In 2023, the U.S. Department of Veterans Affairs (VA) conducted a fit-for-purpose systematic literature review to assess the potential health effects of occupational exposure to jet fuels used by the Armed Forces. Due to significant data gaps in the existing occupational epidemiologic research, it was not possible to draw firm conclusions on the association between jet fuel exposure and any health outcome. To address these gaps, VA conducted an expanded review that incorporated other epidemiologic studies, as well as animal toxicological and mechanistic studies, providing a comprehensive assessment and a descriptive weight-of-evidence evaluation to characterize the potential noncarcinogenic effects of exposure to jet fuel. Methods: VA conducted a fit-for-purpose systematic review, adapting the Environmental Protection Agency’s (EPA) Integrated Risk Information System (IRIS) methodology to assess the possible health effects associated with jet fuel exposure. The review focused on human (military, occupational, and environmental) exposures, as well as animal and mechanistic evidence within several health categories. All relevant human and animal studies underwent quality evaluations. Given the limited epidemiologic data and VA’s aim for inclusivity, epidemiologic studies rated uninformative were considered in the synthesis. Results: The literature search conducted through January 2024 yielded 4,191 unique references. Title/abstract screening identified 610 potentially relevant studies, of which 259 met eligibility criteria following full-text review. Of the 259 references, 33 were unique primary epidemiologic studies, 109 were unique animal toxicological studies, and 111 were mechanistic studies. Reviews (43) and case reports (17) provided supporting information. Epidemiologic evidence was determined to be slight for neurological, cognitive, and behavioral health outcomes based on consistent evidence of short- and long-term hearing and memory impairment, depressive symptoms following jet fuel exposure. Similarly, epidemiologic evidence was slight for respiratory health outcomes, as indicated by modulation of lung function. For other health outcomes (i.e., immune, hepatic, renal, cardiovascular, and hematologic), epidemiologic evidence was determined to be indeterminate. Animal toxicological evidence was determined to be moderate for neurological, respiratory, immunological, and renal health outcomes, as indicated by aberrant neurotransmitter levels and decreased auditory function, lung toxicity, immunosuppression, and altered kidney histopathology, respectively. Hematologic and hepatic animal toxicological evidence was determined to be slight, as indicated by significantly altered red blood cell, hematocrit, and hemoglobin levels and altered hepatic histopathology, respectively. Toxicological evidence for cardiovascular health outcomes cardiovascular was determined to be indeterminate. For some health outcomes, mechanistic studies provided additional evidence supporting exposure-outcome relationships. The health outcome categories classified as indeterminate for both the epidemiologic and animal toxicological evidence streams were due to the limited available scientific evidence and considerable uncertainty in reported data. Conclusions: Considering the available epidemiologic, animal toxicological, and mechanistic studies, evidence indicates it is likely that jet fuel exposure causes aberrant neurological, respiratory, immunological, hepatic, and renal health outcomes in humans. Due to limited scientific evidence, evidence suggests that jet fuel exposure might cause aberrant hematological effects in humans. Cardiovascular effects were evaluated in very few studies, and although some effects were observed, considerable uncertainty remains due to the lack of confidence in the human studies and sparse findings in animal studies. Therefore, evidence of a relationship between jet fuel exposure and cardiovascular effects was determined to be inadequate.