OBJECTIVES: Major amputation may be required when limb-sparing surgery is not possible for musculoskeletal tumors, or has failed. The authors aimed to assess the function and health-related quality of life (HRQoL) after major lower extremity amputation due to musculoskeletal tumors. METHODS: Thirteen non-consecutive adult patients (two men and 11 women; mean age 66 years) who had been fitted with a prosthesis after having undergone major lower extremity amputation due to a tumor. Participants completed a general health survey on a 0-100mm (best-worst) visual analog scale, the Locomotor Capabilities Index 5, and the 15D HRQoL instrument at a median of five years after amputation. Twenty-four major lower extremity trauma patients who had their amputated limb fitted with a prosthesis served as HRQoL controls. RESULTS: The mean (SD) general health was 23/100 (13), 15D Mobility dimension was 2.2/5 (0.6) and locomotor capability was 44/100 (13). The mean 15D index was 0.85 (0.11) and that of the control group 0.87 (0.11). Both scores were somewhat lower than those usually observed in similar aged general population (around 0.90). CONCLUSIONS: Function after major lower extremity amputation due to musculoskeletal tumors is good among patients who had undergone succesful prosthetic fitting, and the HRQoL is slightly lower than similar aged general population but comparable to that of major lower extremity trauma amputees.