Little research has described the long-term health outcomes of patients who had combat-related amputations or leg-threatening injuries. We conducted retrospective analysis of Department of Defense and Department of Veterans Affairs health data for lower extremity combat-injured patients with (1) unilateral amputation within 90 days postinjury (early amputation, n = 440), (2) unilateral amputation more than 90 days postinjury (late amputation, n = 78), or (3) leg-threatening injuries without amputation (limb salvage, n = 107). Patient medical records were analyzed for four years postinjury. After adjusting for group differences, early amputation was generally associated with a lower or similar prevalence for adverse physical and psychological diagnoses (e.g., pain, osteoarthritis, posttraumatic stress disorder) versus late amputation and/or limb salvage. By contrast, early amputation was associated with an increased likelihood of osteoporosis during the first year postinjury. The prevalence of posttraumatic stress disorder increased for all patient groups over four years postinjury, particularly in the second year. The different clinical outcomes among combat extremity injured patients treated with early amputation, late amputation, or limb salvage highlight their different healthcare requirements. These findings can inform and optimize the specific treatment pathways that address the physical and psychological healthcare needs of such patients over time.