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Objective The aims of this study were to review the demographic details of those who have undergone lower limb amputation (LLA) surgery in Central Australia and determine the region-specific age-adjusted incidence rate of LLA. Methods A retrospective audit of service users who underwent LLA in a Central Australian hospital from 2012 to 2017 was undertaken. Demographic, operative and postoperative outcomes data were collected. The age-adjusted incidence rate of LLA was determined using the direct method. Demographic data were analysed using descriptive parametric analysis. Results In the period 2012-17, 166 service users underwent a total of 291 amputations in 231 episodes of care (hospital admissions). The age-adjusted incidence rate of LLA was 87.4 per 100000 for females and 104.6 per 100000 for males in this region. In total, 84% (n=140) of those requiring amputation surgery identified as Aboriginal Australians (P<0.001), 54% (n=75) of whom were female. Aboriginal Australians who underwent LLA were, on average, 13 years younger and were more likely to have type 2 diabetes (P<0.001) and require renal dialysis (P<0.001) than the non-Aboriginal Australian cohort. Of the Aboriginal Australians who underwent LLA, 82% (n=103) lived very remotely (>100km from the central town's centre), compared with 23% of non-Aboriginal Australians (P<0.001). In addition, 46% (n=64) of Aboriginal Australians who underwent LLA required renal dialysis. Those requiring renal dialysis were more likely to require subsequent amputation (P=0.014) and had a higher mortality rate following amputation (P=0.031). Partial foot amputation was the most common level of amputation in Central Australia (38%). Conclusions Central Australia appears to have the highest incidence rate of LLA for any region in Australia, with Aboriginal Australians, particularly females and those undergoing renal dialysis, being disproportionately represented. Further studies should aim to determine targeted, culturally safe and successful methods of diabetic foot ulcer prevention, early detection and management with a view to reducing the high amputation rates for these cohorts. What is known about the topic? Large health inequalities between Aboriginal and non-Aboriginal Australians exist. Aboriginal Australians are currently fourfold as likely as non-Aboriginal Australians to have type 2 diabetes (T2D), increasing their risk of LLA. There is a geographical variance in the incidence of LLA in Australia; the Northern Territory is overrepresented, with rates two- to threefold higher than that of the national average. Regional incidence rates are not currently known. What does this paper add? This study showed that the age-adjusted incidence rate for LLA in Central Australia is significantly higher than in other regions in Australia. Most LLA surgeries undertaken in Central Australia were performed for Aboriginal Australians who have T2D, with a disproportionate representation of females and those requiring renal dialysis. What are the implications for practitioners? This study shows that there is a need for further research and preventative measures to address the high rates of LLA among Aboriginal Australians, particularly for females and those with renal impairment. These groups could benefit from targeted, culturally safe approaches to early identification, referral and management of lower limb ulceration by relevant service providers.