Rates of cardiovascular and diabetes-related complications are generally decreasing. Whether a similar decline has occurred with lower extremity amputations remains poorly characterized. The aim of this study was to examine secular trends in the rate of lower extremity amputations among patients with diabetes and peripheral artery disease (PAD), within a single-payer regional health care system. The study cohort included all individuals 40 years old who underwent diabetes- or PAD-related lower limb amputation in Ontario, Canada (population, 13.6 million), between April 2005 and March 2016. Patients and amputations were identified through deterministic linkage of administrative health databases including inpatient and outpatient records. Quarterly rates (per 100,000 individuals 40 years old) of minor or major amputation as well as of major amputation alone were established. Time-series analyses were conducted using exponential smoothing models to characterize secular trends. A total of 19,961 patients underwent minor or major lower extremity amputations, of whom 12,755 (64%) underwent a major amputation. A total of 18,745 (94%) patients had PAD, 16,366 (82%) had diabetes, and 15,150 (76%) had both PAD and diabetes. The rate of any amputation initially declined between 2005Q2 and 2010Q4 but increased again by 2016Q1 (Fig 1), with PAD-related minor or major amputations following a similar trend (Fig 1). A significant increase was observed in the rate of any amputation among patients with diabetes and those with diabetes and PAD (Fig 1). Whereas the rates of major amputations decreased, although not significantly, among PAD patients, diabetes-related major amputations did not decrease (Fig 2). Diabetes-related lower extremity amputations have increased during the last decade. These data support renewed efforts to prevent and to decrease the burden of limb loss among patients with diabetes.Fig 2Peripheral artery disease (PAD) or diabetes-related major lower extremity amputations in Ontario, Canada.View Large Image Figure ViewerDownload Hi-res image Download (PPT)