OBJECTIVES: The study assessed the clinical and functional outcomes of transfemoral amputations following TKA complications, shedding light on a procedure often considered in extreme cases. METHODS: In this retrospective study, six patients undergoing above-knee amputation due to TKA complications were analysed. Diagnosis of periprosthetic joint infection relied on clinical presentation and the Musculoskeletal Infection Society Definition (2011). Patient demographics, comorbidities, and surgical interventions were meticulously recorded. The study aimed to contribute valuable insights into the intricacies of managing complications post-TKA. RESULTS: The study cohort, constituting 0.002% of total TKA cases, exhibited a mean age of 78.8 years. Comorbidities, predominantly diabetes, were prevalent. The duration between TKA and amputation averaged 6.3 years. Surgical interventions, including revisions, debridements, and aspirations, were numerous, reflecting the complexity of managing complications. All patients underwent above-knee amputation using a single-stage approach, with careful consideration of the surgical site's condition. Post-amputation care, including stump care and prosthetic leg options, was tailored to individual patients' needs. Patients were diligently followed for a minimum of 12 months. Stump wounds healed without requiring revisions, and prosthetic limbs were successfully applied to three patients. Mobility status and disability scores, evaluated through the Sickness Impact Profile (SIP), showed significant improvement. CONCLUSION: The study highlights periprosthetic joint infection as the primary cause of multiple failed procedures leading to amputation. Microbiological findings identified common pathogens, including Staphylococcus aureus and Pseudomonas aeruginosa. Challenges posed by biofilm formation underscored the complexities of antibiotic treatment. Transfemoral amputation emerges as a feasible option for patients with multiple failed TKAs, particularly in cases of persistent infection. The decision-making process should encompass a thorough consideration of the number of failed procedures, cost-benefit analysis, and various psychosocial and economic factors. Further research and extensive multicentric studies are imperative to validate and expand upon these findings.