Between 1996 and 2013, there was a 54% decrease in the incidence of diabetes-related end-stage renal disease (ESRD-DM) in American Indian and Alaska Native (AI/ AN) populations. This decline has occurred since the Special Diabetes Program for Indians (SDPI) was established in 1997. We estimate that the decrease in ESRD-DM incidence resulted in 2,200 to 2,600 fewer cases and $436 to $520 million of savings to Medicare over a ten-year period, depending on assumptions of what the incidence rate would have been in the absence of diabetic care improvements. Additional savings from the program may accrue to the Indian Health Service and other payers by preventing diabetes and other complications of diabetes such as retinopathy or hospitalizations. Although it is not possible to determine with certainty how much of the decline in ESRD-DM is attributable to SDPI, nothing else has impacted diabetes resources across Indian health care systems as much as SDPI over the past 20 years and improvements in related outcomes in the Al/AN population far surpass those observed in other races.