OBJECTIVE: Nontraumatic lower extremity amputation (NLEA) is a complication of end-stage renal disease (ESRD) and diabetes. Although recent data show that NLEA rates in the U.S. ESRD population are declining overall, trends in diabetes and diabetes subgroups remain unclear. RESEARCH DESIGN AND METHODS: We estimated annual rates of NLEA hospitalizations during 2000-2015 among >2 million adults (≥18 years) with ESRD from the U.S. Renal Data System. Age, sex, and race-adjusted NLEA rates were stratified by diabetes status, age, sex, race, and level of amputation (toe, foot, below the knee, and above the knee). Time trends were assessed using Joinpoint regression with annual percent changes (APC) reported. RESULTS: Among adults with diabetes, NLEA rates declined 43.8% between 2000 and 2013 (from 7.5 to 4.2 per 100 person-years; APC -4.9, P < 0.001) and then stabilized. Among adults without diabetes, rates of total NLEAs declined 25.5% between 2000 and 2013 (from 1.6 to 1.1; APC -3.0, P < 0.001) and then stabilized. These trends appear to be driven by a slowing or stagnation in declines of minor NLEAs (toe and foot) in more recent years, while major NLEAs (above the knee) continue to decline. CONCLUSIONS: Despite an initial period of decline, this analysis documents a stall in progress in NLEA trends in recent years in a high-risk population with both ESRD and diabetes. Increased attention to preventive foot care in the ESRD population should be considered, particularly for those with diabetes.