Background and aims: The purpose of this study was to assess the incidence and risk factors for non-traumatic lower extremity amputation (LEA) in patients on haemodialysis (HD). Methods: We investigated our HD population attending our clinic between Jan 1988 and Dec 2002, who had had LEA. Uni- and multivariate analyses were used to determine association of LEA with demographic characteristics such as diabetes, hypertension, smoking, myocardial infarction, stroke, dyslipidaemia, haematocrit, urea, creatinine, calcium, phosphorous, parathyroid hormone (PTH) and albumin levels. Results: Of 516 patients, 20 (3.9%) underwent 32 amputations; 21 major and 71 minor. The incidence was 1.1 amputees/100 p-years. There were 11 (10.8%) diabetics and 9 (2.2%) non-diabetics; incidence of 4.2 and 0.6 amputees/100 p-years, respectively. Non-diabetic amputees were older than non-amputees: 68.9 vs 58.2 years (p = 0.013) and had been on HD longer: 71.4 +/- 44 vs 42 +/- 37 months (p = 0.019). There were 60% deaths within the first year of amputation and the causes were 60% cardiovascular. Univariate analysis indicated significant association of LEA with ageing, diabetes, smoking, myocardial infarction, stroke, high cholesterol, and low PTH levels. Multivariate Cox regression identified independent associations of amputation with diabetes, previous myocardial infarction and stroke and/or transient ischaernic attack. Conclusions: The incidence of LEA in HD patients is very high and is associated with diabetes and previous cardiovascular events. Advanced age and longer time on HD are factors related to LEA in non-diabetics. With increasing numbers of diabetics and older people on HD, new strategies are needed for peripheral arterial disease management so as to avoid its progression to critical ischaemia.