Dialysis therapy has remarkably evolved through the innovation in dialyzers and hemodialysis modalities, enhancing patients’ quality of life. The efficacy of dialysis can be determined by measuring the reduction ratio (RR) of middle molecules, such as alpha 1-microglobulin (A1M). In this study, we tested a high-flux dialyzer, BIOPURE (Biorema) 260 HF, with a surface area (SA) of 2.6 m2, in terms of A1M removal and concurrent albumin loss in dialysate while receiving high-flux hemodialysis (HF-HD) and post-dilution online hemodiafiltration (OL-HDF). This crossover study comprised 25 patients who received a session of HF-HD using the BIOPURE (Biorema) 260 H, followed by a session of post-dilution OL-HDF. A washout period of 2 weeks was instilled between the two sessions, during which the patients received HF-HD using high-flux dialyzers (maximum SA 2.0 m2). All patients’ hourly dialysate albumin and pre/post dialysis concentrations of A1M were measured. The dialyzer used in this study resulted in significantly higher A1M RR of 41.9±7.93% with HDF than with HF-HD 27.12±7.65% (p<0.001), and a median cumulative dialysate albumin loss of 2.97g (IQR 1.98 – 3.37), and 0.67g (IQR 0.49 – 1.13) with HDF and HF-HD, respectively. In conclusion, the dialyzer BIOPURE (Biorema) 260 HF (SA 2.6 m2) is efficient in eliminating A1M, especially with OL-HDF compared to HF-HD, with acceptable albumin loss in the dialysate.