Background Rheopheresis is a double-filtration plasmapheresis that removes high-molecular-weight molecules from the plasma and thereby lowers blood viscosity. This treatment has been proposed in hemodialysis (HD) patients for chronic limb-threatening ischemia (CLTI), but very few studies have evaluated the usefulness of this technique. Principal Objective To assess 1-year amputation-free survival (AFS) of HD patients suffering from CLTI treated by rheopheresis. Material and Method We conducted a retrospective study of 28 consecutive HD patients treated by rheopheresis in three French dialysis centers between 1 February 2017 and 30 April 2019 in two indications resulting from CLTI, namely chronic ulceration or recent minor amputation with delayed healing. Results One-year AFS rate reached 53.6 (-19.8; +16.3)%. One-year overall survival rate reached 67.9 (-20.5; +13.1)%. Main causes of death were infections and related to palliative care implying reduction or withdrawal of regular dialysis treatment. Hypotension episodes were the main rheopheresis adverse events with a prevalence rate of 13.5%. Rheopheresis sessions significantly reduced fibrinogen, C-reactive protein, alpha 2-macroglobulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, IgM, and estimated plasma viscosity (P < .0001). Conclusion Rheopheresis may improve clinical outcomes of CLTI in HD patients. The assessment of rheopheresis effectiveness needs to be confirmed by a multicenter randomized controlled trial, such as the ongoing project in France (RHEO-PAD, NCT: 03975946).