Introduction: New generation helixone dialyzers has recently been developed as part of the ongoing effort to improve dialyzer hemocompatibility and avoid adverse reactions to synthetic dialyzers. This study aimed to assess the performance and albumin loss of this new dialyzer series in hemodiafiltration and compare it with the previous generation helixone series. Material and methods: A prospective study was conducted in 19 patients. Each patient underwent eight dialysis sessions with the same routine dialysis parameters; only the dialyzer varied: FX60 CorDiax, FX CorAL 60, FX600 CorDiax, FX CorAL 600, FX80 CorDiax, FX CorAL 80, FX800 CorDiax, and FX CorAL 800. The reduction ratios (RR) of urea, creatinine, (32-microglobulin, 2-microglobulin, myoglobin, kappa-free immunoglobulin light chains (KFLC), prolactin, a1-microglobulin, 1-microglobulin, a1 1-acid glycoprotein, lambda immunoglobulin light chains (XFLC), and albumin were compared intra-individually. Dialysate albumin loss was also measured. Results: All treatments were well tolerated. The mean amount of replacement fluid ranged from 31 to 34 litres. Comparison of dialysis treatments showed no differences between small molecules and even up to those the size of (32-microglobulins. 2-microglobulins. Little differences were found between myoglobin, KFLC, prolactin, a1-microglobulin, 1-microglobulin, and XFLC RRs, and only FX80 CorDiax was slightly superior to the others. Mean dialysate albumin losses were similar, with less than 2.5 grams lost in each dialyzer. The FX80 CorDiax showed slightly higher global removal scores than the other dialyzers evaluated, except for FX CorAL 800. Conclusion: The new generation helixone dialyzers series has been updated to minimise the risk of adverse reactions, while maintaining the effectiveness and albumin loss achieved by the previous most advanced helixone generation. (c) 2024 Published by Elsevier Espana, S.L.U. on behalf of Sociedad Espanola ola de Nefrolog & imath;a. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).