Purpose: Anemia in chronic kidney disease dialysis patients is a complex syndrome involving many causes. Adequate dialysis can contribute to its correction through many mechanisms, including the removal of molecules that may inhibit erythropoiesis. The aim of this pilot study was to evaluate the effect on renal anemia of two synthetic, high-flux dialyzers (polynephron vs. high-flux polysulphone). Methods: 20 dialysis patients (11 male; mean age: 72 years) were randomly assigned and studied for 6 months. There were 2 dropouts in each group. Each patient underwent 3 hemodialysis treatments per week without any difference in dialysis prescription. At T = 0 and T = 6 (after 6 months), instantaneous plasma clearances and reduction rates of small solutes, β2-microglobulin protein (β2-μ); hemoglobin (Hb), and iron pattern were measured. The effect on anemia was evaluated by calculating the Erythropoesis Stimulating Agent (ESA) doses and the Erythropoietin Resistance Index (ERI). Results: Kt/V increased between T0 and T6 in both groups. β2-μ pre-dialysis levels significantly decreased between T0 and T6 in both dialyzer groups (pConclusions: High-flux filters improved Hb levels, although only significantly in the polynephron group, suggesting a possible different effect. The results should be interpreted with caution and tested in an appropriately powered, large, prospective, randomized control trial.