BACKGROUND: After septic failure of total knee arthroplasty (TKA) and multiple revision operations resulting in impaired function, bone and/or soft-tissue damage a reconstruction with a revision arthroplasty might be impossible. Salvage procedures to regain mobility and quality of life are an above-the-knee amputation or knee arthrodesis. The decision process for the patient and surgeon is difficult and data comparing arthrodesis versus amputation in terms of function and quality of life are scarce. The purpose of this study was to analyse and compare the specific complications, functional outcome and quality of life of above-the-knee amputation (AKA) and modular knee-arthrodesis (MKA) after septic failure of total knee arthroplasty. METHODS: Eighty-one patients treated with MKA and 32 patients treated with AKA after septic failure of TKA between 2003 and 2012 were included in this cohort study. Demographic data, comorbidities, pathogens and complications such as re-infection, implant-failure or revision surgeries were recorded in 55MKA and 20AKA patients. Functional outcome with use of the Lower-Extremity-Functional-Score (LEFS) and the patients reported general health status (SF-12-questionnaire) was recorded after a mean interval of 55 months. RESULTS: A major complication occurred in more than one-third of the cases after MKA and AKA, whereas recurrence of infection was with 22% after MKA and 35% after AKA the most common complication. Patients with AKA and MKA showed a comparable functional outcome with a mean LEFS score of 37 and 28 respectively (p = 0.181). Correspondingly, a comparable physical quality of life with a mean physical SF-12 of 36 for AKA patients and a mean score of 30 for MKA patients was observed (p = 0.080). Notably, ten AKA patients that could be fitted with a microprocessor-controlled-knee-joint demonstrated with a mean LEFS of 56 a significantly better functional outcome than other amputee patients (p < 0.01) or MKA patients (p < 0.01). CONCLUSION: Naturally, the decision process for the treatment of desolate situations of septic failures following revision knee arthroplasty is depending on various factors. Nevertheless, the amputation should be considered as an option in patients with a good physical and mental condition.