Background Adults with end-stage renal disease are at increased risk of foot ulceration and lower extremity amputation. However, the central determinants of lower limb injury and loss are incompletely understood. Methods We conducted a systematic review of non-randomized studies that quantified the major risk factors for foot ulceration and amputation in adults treated with dialysis and analysed patient populations in which risks were greatest. Random-effects meta-analysis was used to generate summary estimates. Results Thirty studies (48 566 participants) were identified. Risk factors for foot ulceration and amputation included previous foot ulceration (odds ratios, OR, 17.56 and 70.13), peripheral arterial disease (OR, 7.52 and 9.12), diabetes (OR, 3.76 and 7.48), peripheral neuropathy (OR, 3.24 and 3.36) and coronary artery disease (OR, 3.92 and 2.49). Participants with foot ulceration or amputation had experienced a longer duration of diabetes (mean difference, MD, 4.04 and 6.07 years) and had lower serum albumin levels (MD, -0.23 and -0.13 g/dL). Risk factors for foot ulceration also included retinopathy (OR, 3.03), previous amputation (OR, 15.50) and higher serum phosphorus levels (MD, 0.40 mg/dL), while risk factors for amputation also included male sex (OR, 1.50), current smoking (OR, 2.26) and higher glycated haemoglobin levels (MD, 0.75 ). Conclusions Dialysis patients who have markedly higher risks of ulceration or amputation include those with previous foot ulceration or amputation, peripheral neuropathy, diabetes or macrovascular disease. The temporal relationship between these risk factors and the development of foot ulceration and/or limb loss is uncertain and requires further study. Stable estimates of the key risk factors for ulceration and amputation can inform the design of future trials investigating clinical interventions to reduce the burden of lower limb disease in the dialysis population.