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Objective: Major lower extremity (MLE) amputation is a common procedure that results in a profound change in a patient's life. We sought to determine the association between social support and outcomes after amputation. We hypothesized that patients with greater social support will have better post amputation outcomes., Methods: From November 2011 to May 2013, we conducted a cross-sectional, observational, multicenter study. Social integration was measured by the social integration subset of the Short Form Craig Handicap Assessment and Reporting Technique. Systemic social support was assessed by comparing a United States and Tanzanian population. Walking function was measured using the 6-minute walk test and quality of life (QoL) was measured using the EuroQol-5D., Results: We recruited 102 MLE amputees. Sixty-three patients were enrolled in the United States with a mean age of 58.0. Forty-two (67%) were male. Patients with low social integration were more likely to be unable to ambulate (no walk 39% vs slow walk 23% vs fast walk 10%; P = .01) and those with high social integration were more likely to be fast walkers (no walk 10% vs slow walk 59% vs fast walk 74%; P = .01). This relationship persisted in a multivariable analysis. Increasing social integration scores were also positively associated with increasing QoL scores in a multivariable analysis (β, .002; standard error, 0.0008; P = .02). In comparing the United States population with the Tanzanian cohort (39 subjects), there were no differences between functional or QoL outcomes in the systemic social support analysis., Conclusions: In the United States population, increased social integration is associated with both improved function and QoL outcomes among MLE amputees. Systemic social support, as measured by comparing the United States population with a Tanzanian population, was not associated with improved function or QoL outcomes. In the United States, steps should be taken to identify and aid amputees with poor social integration., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)