Growing evidence suggests the superiority of on-line hemodiafiltration (HDF) compared with the conventional hemodialysis technique in many aspects; however, on-line HDF is still not used worldwide, including in Southeast Asia. The purpose of this study is to compare various clinical outcomes between on-line HDF and high-flux hemodialysis (HFHD). This was a single-center three-year prospective observational study that demonstrated the clinical parameters after switching from HFHD to on-line HDF in 22 HDF patients, whose average age was 58.1 +/- 13.3 years. The incidence of intradialytic undesired events, including hypotension, decreased and an apparent increase in appetite and an improvement in overall well-being were recorded by most patients after switching to on-line HDF. The data for dry weight, body mass index, and normalized protein nitrogen appearance, which represent nutritional status, showed a significant improvement while still maintaining a satisfactory albumin level. The adequacy in terms of urea reduction ratio significantly increased. The serum predialysis beta(2)-microglobulin levels were reduced by 25.7% from 31.1 +/- 3.1 to 23.1 +/- 4.8 mg/L (P < 0.05) at six months and remained constant during the three years of follow-up. The patients' lipid profile was well controlled, and the mean C-reactive protein value was still maintained in the normal range. In conclusion, our three-year experience showed that on-line HDF is a well-tolerated treatment with a lower incidence of intradialytic undesired events. The potential benefits may include the effective removal of higher molecular weight uremic toxins and an improved nutritional status, along with a low inflammatory state.