A total of 3 patients, a female aged 66 years, a male aged 67 years and a female aged 82 years, presented with rest pain or gangrene of their lower extremities as a result of critical limb ischemia (CLI). Radiographic studies showed non-reconstructable arterial obstructive disease in the 66-year-old female patient, who underwent an uncomplicated primary amputation and subsequent rehabilitation. Bypass surgery was initially performed in the male patient. However, failed reconstruction and progression of ischaemia necessitated transfemoral amputations to be performed, which was followed by impaired rehabilitation. In the 82-year-old female patient gangrene was the indication for primary amputation. She died due to progressive sepsis following surgery. In about 40% of patients with CLI, major lower extremity amputation is the ultimate solution. The morbidity, mortality and rehabilitation potential in CLI and the factors that influence these outcomes are discussed. The most clinically relevant determinants of morbidity, mortality and rehabilitation following major lower extremity amputation are comorbidity, age, preoperative mobility and amputation level.