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Patients with end-stage renal disease (ESRD) who receive dialysis are at high risk of lower extremity amputation. Recent studies indicate decreasing rates of lower extremity amputation in non-ESRD populations, but contemporary data for patients with ESRD who receive dialysis are lacking.To assess rates of lower extremity amputation among patients with ESRD who receive dialysis during a recent 15-year period; to analyze whether those rates differed by age, sex, diabetes, or geographic region; and to determine 1-year mortality rates in this population after lower extremity amputation.This retrospective study of 3 700 902 records obtained from a US national registry of patients with ESRD who receive dialysis assessed cross-sectional cohorts for each calendar year from 2000 through 2014. Adult patients with prevalent ESRD treated with hemodialysis or peritoneal dialysis covered by Medicare Part A and B on January 1 of each cohort year were included. Data analysis was conducted from August 2017 to April 2018.Age, sex, diabetes, and hospital referral region.Annual rates per 100 person-years of nontraumatic major (above- or below-knee) and minor (below-ankle) amputations.For each annual cohort, there were fewer women (47.5% in 2000, 46.2% in 2005, 44.9% in 2010, and 44.0% in 2014) than men, more than half the patients were white individuals (58.1% in 2000, 56.9% in 2005, 56.9% in 2010, and 56.7% in 2014), and a small proportion were employed (13.9% in 2000, 15.1% in 2005, 16.1% in 2010, and 16.5% in 2014). The rate of lower extremity amputations for patients with ESRD who receive dialysis decreased by 51.0% from 2000 to 2014, driven primarily by a decrease in the rate of major amputations (5.42 [95% CI, 5.28-5.56] in 2000 vs 2.66 [95% CI, 2.59-2.72] per 100 person-years in 2014). Patients with diabetes had amputation rates more than 5 times as high as patients without diabetes. Patients younger than 65 years had higher adjusted amputation rates than older patients, and men had consistently higher adjusted amputation rates than women. Adjusted 1-year mortality rates after lower extremity amputation for patients with ESRD who receive dialysis decreased from 52.2% (95% CI, 50.9%-53.4%) in 2000 to 43.6% (95% CI, 42.5%-44.8%) in 2013. In general, amputation rates decreased among all regions from 2000 to 2014, but regional variability persisted across time despite adjustment for differences in patient demographics and comorbid conditions.Although rates of lower extremity amputations among US patients with ESRD who receive dialysis decreased by 51% during a recent 15-year period, mortality rates remained high, with nearly half of patients dying within a year after lower extremity amputation. Our results highlight the need for more research on ways to prevent lower extremity amputation in this extremely high-risk population.