Background: The principal aims of this study were to examine functional outcomes following trauma-related lower-extremity amputation and to compare outcomes according to the amputation levels. We hypothesized that above-the-knee amputations would result in less favorable outcomes than would through-the-knee or below-the-knee amputations. A secondary aim was to examine the factors, in addition to amputation level, that influence outcome, including the type of soft-tissue coverage, selected patient characteristics, and the technological sophistication of the prosthetic device. Methods: A cohort of 161 patients who had undergone an above-the-ankle amputation at a trauma center within three months following the injury was followed prospectively at three, six, twelve, and twenty-four months after the injury. The Sickness Impact Profile, a self-reported measure of functional status, was used as the principal measure of outcome. Secondary outcomes included pain; degree of independence in transfers, walking, and climbing stairs; self-selected walking speed; and the physician's satisfaction with the clinical, functional, and cosmetic recovery of the limb. Longitudinal multivariate regression techniques were used to determine whether outcomes differed according to the level of amputation after we controlled for covariates. Results: There was no significant difference in the scores on the Sickness Impact Profile between the patients treated with above-the-knee and those treated with below-the-knee amputation. However, patients with a below-the-knee amputation performed better than did patients with an above-the-knee amputation on the timed test for walking speed (p = 0.04). Patients with a through-the-knee amputation had worse regression-adjusted Sickness Impact Profile scores (p = 0.05) and slower self-selected walking speeds (p = 0.004) than did patients with either a below-the-knee or an above-the-knee amputation. Differences according to the level of amputation were most pronounced for physical function. In general, physicians were less satisfied with the clinical, cosmetic, and functional recovery of the patients with a through-the-knee amputation. Except for problems encountered with insufficient gastrocnemius coverage of the stump in many patients with a through-the-knee amputation, neither the soft-tissue coverage nor the technological sophistication of the prosthesis correlated with outcome. Conclusions: Severe disability accompanies above-the-ankle lower-extremity amputation following trauma, regardless of the level of amputation. Clinicians should critically evaluate the need for a through-the-knee amputation in patients with a traumatic injury. The results of this study also underscore the need for controlled studies that examine the relationship between the type and fit of prosthetic devices and functional outcomes. Level of Evidence: Prognostic study, Level I-1 (prospective study).