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Background: Non-traumatic lower limb amputation rates are rising worldwide, resulting in increased hospitalisations and use of rehabilitation services. This study aimed to identify key comorbidities associated with prolonged length of stay or decreased functional gain for episodes receiving inpatient rehabilitation following non-traumatic lower limb amputation. Methods: Prospectively collected data submitted to the Australasian Rehabilitation Outcomes Centre were analysed. The cohort comprised episodes for patients (aged ≥18 years) discharged from inpatient rehabilitation between 1 July 2013 and 30 June 2018 following a non-traumatic lower limb amputation. Results: The cohort included 5074 episodes with an average age of 66.3 years and the majority being male (71.7%). Comorbidities affecting the ability to participate in rehabilitation were reported for 65.4% of episodes, most commonly diabetes mellitus (50.3%), cardiac disease (33.5%), and respiratory disease (10.1%). These comorbidities were associated with a prolonged length of stay and reduced functional improvement. Conclusion: This study showed comorbidities contribute to prolonged length of stay and poorer functional outcomes among those undergoing inpatient rehabilitation following non-traumatic lower limb amputation. Future research should focus on strategies to address these comorbidities to help improve patient outcomes and reduce healthcare costs. What is known about the topic? It is known that the presence of comorbidities contributes to lower limb amputation; however, the effect that comorbidities have on inpatient rehabilitation outcomes is not well reported. What does this paper add? This study identified five comorbidities (diabetes mellitus, cardiac disease, respiratory disease, renal failure with dialysis, and mental health problems) associated with prolonged length of stay and decreased functional outcomes following inpatient rehabilitation for non-traumatic lower limb amputation. What are the implications for practitioners? Our findings suggest practitioners should focus on strategies to address these comorbidities to help improve functional outcomes, reduce length of stay, and reduce healthcare costs. [ABSTRACT FROM AUTHOR]