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The study was performed to examine the hypothesis that functional outcomes following major lower-extremity trauma sustained in the military would be similar between patients treated with amputation and those who underwent limb salvage.This is a retrospective cohort study of 324 service members deployed to Afghanistan or Iraq who sustained a lower-limb injury requiring either amputation or limb salvage involving revascularization, bone graft/bone transport, local/free flap coverage, repair of a major nerve injury, or a complete compartment injury/compartment syndrome. The Short Musculoskeletal Function Assessment (SMFA) questionnaire was used to measure overall function. Standard instruments were used to measure depression (the Center for Epidemiologic Studies Depression Scale), posttraumatic stress disorder (PTSD Checklist-military version), chronic pain (Chronic Pain Grade Scale), and engagement in sports and leisure activities (Paffenbarger Physical Activity Questionnaire). The outcomes of amputation and salvage were compared by using regression analysis with adjustment for age, time until the interview, military rank, upper-limb and bilateral injuries, social support, and intensity of combat experiences.Overall response rates were modest (59.2%) and significantly different between those who underwent amputation (64.5%) and those treated with limb salvage (55.4%) (p = 0.02). In all SMFA domains except arm/hand function, the patients scored significantly worse than population norms. Also, 38.3% screened positive for depressive symptoms and 17.9%, for posttraumatic stress disorder (PTSD). One-third (34.0%) were not working, on active duty, or in school. After adjustment for covariates, participants with an amputation had better scores in all SMFA domains compared with those whose limbs had been salvaged (p < 0.01). They also had a lower likelihood of PTSD and a higher likelihood of being engaged in vigorous sports. There were no significant differences between the groups with regard to the percentage of patients with depressive symptoms, pain interfering with daily activities (pain interference), or work/school status.Major lower-limb trauma sustained in the military results in significant disability. Service members who undergo amputation appear to have better functional outcomes than those who undergo limb salvage. Caution is needed in interpreting these results as there was a potential for selection bias.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.