Background: Diabetes-related lower limb amputations (LLAs) are a major complication that can be reduced by employing multidisciplinary center frameworks such as the Toe and Flow model (TFM). In this study, we investigate the LLAs reduction efficacy of the TFM compared to the standard of care (SOC) in the Canadian health-care system. Methods: We retrospectively reviewed the anonymized diabetes-related LLA reports (2007-2017) in Calgary and Edmonton metropolitan health zones in Alberta, Canada. Both zones have the same provincial health-care coverage and similar demographics; however, Calgary operates based on the TFM while Edmonton with the provincial SOC. LLAs were divided into minor and major amputation cohorts and evaluated using the chisquare test, linear regression. A lower major LLAs rate was denoted as a sign for higher efficacy of the system. Results: Although LLAs numbers remained relatively comparable (Calgary: 2238 and Edmonton: 2410), the Calgary zone had both significantly lower major (45%) and higher minor (42%) amputation incidence rates compared to the Edmonton zone. The increasing trend in minor LLAs and decreasing major LLAs in the Calgary zone were negatively and significantly correlated (r ¼-0.730, p ¼ 0.011), with no significant correlation in the Edmonton zone. Conclusions: Calgary’s decreasing diabetes-related major LLAs and negative correlation in the minor-major LLAs rates compared to its sister zone Edmonton, provides support for the positive impact of the TFM. This investigation includes support for a modernization of the diabetes-related limb preservation practice in Canada by implementing TFMs across the country to combat major LLAs. (J Am Podiatr Med Assoc 111(4): 1-10, 2021).