In spite of the better efficiency of on-line hemodiafiltration (HDF) compared with conventional hemodialysis (HD), it is relatively expensive. The aim of this study was to assess the advantages in the biochemical, hemodynamic and clinical effects in uremic patients treated with on-line HDF and with different frequencies of combination high-flux HD. One hundred eleven patients were divided into four groups receiving different frequencies of on-line HDF (thrice, twice, once per week) and high-flux HD. Hemodynamic parameters including maximum drop of systolic blood pressure, episodes of symptomatic hypotension and mean saline infusion volumes during dialysis were reduced when frequencies of on-line HDF were increased. Significant improvements in urea kinetic were observed when frequencies of on-line HDF were increased. On-line HDF significantly reduced the amount of erythropoietin needed and improved intra- and inter-dialysis symptoms, physical well-being, menstruation and skin pigmentation when frequency of HDF is increased to three time per week. On-line HDF offers a better cardiovascular stability and clinical improvement. Thrice weekly on-line HDF offers a significant benefit when compared with lower frequencies of HDF per week and high-flux HD.