Complications from below knee amputations (BKA), such as wound dehiscence and infections, incur high healthcare costs due to multiple and extended hospitalizations. Due to the significant morbidity still associated with proximal amputations, a careful patient selection process should be considered. This retrospective cohort study aimed to identify risk factors associated with failure of below-knee amputation (BKA), defined as progression to above-knee amputation (AKA), in patients with diabetes. Eligible patients were those who underwent primary BKA due to diabetic complications. Patients were divided into two groups: BKA and failed BKA group. Demographic variables were age, gender, BMI, smoking status, presence of vascular disease, dialysis status, nutritional status, pre-surgery hemoglobin, hemoglobin A1c, culture biopsies and use of antibiotics. Outcome variables included failure (i.e., above-knee amputation) and time to failure. Variables associated with failure of BKA included higher hemoglobin levels, prior vascular procedures, smoking, and perioperative use of oral antibiotics. Notably, oral antibiotics were linked to a higher risk of BKA failure, with patients on oral antibiotics experiencing failure more quickly than those treated with intravenous antibiotics. In addition, in the BKA group, there was a lower percentage of patients treated with PO antibiotics compared to the failed BKA group, 12 % and 19 %, respectively (P = 0.0037). This study highlights that prior vascular procedures and smoking also elevate the risk of BKA failure.