Background: Hemodiafiltration with online preparation of the substitution [online high-flux hemodiafiltration (OHDF)] and hemodiafiltration with prepared bags of substitution (HDF) are important, recently widely used renal replacement therapies in patients with end-stage renal disease. However, there is little information on the comparative impacts of these modalities versus conventional low-flux hemodialysis (HD) on the quality of life (QoL) of HD patients. This study investigates the effect of dialysis modality on QoL in chronic HD patients. Methods: In this prospective, randomized, cross-over, open label study, 24 patients were enrolled. Their age were 62 AE 13.34 years (mean AE SD), with the duration of dialysis of 31 AE 23.28 months (mean AE SD). Five of the patients were women. QoL was measured by the Short-Form Health Survey with 36 questions (SF-36) and subscale scores were calculated. Each patient received HD, OHDF, and HDF for 3 months, with the dialysis modality subsequently being altered. They completed the questionnaire of QoL at the end of each period. Results: There were statistical significant differences in QoL for the total .7) and 40.7 (30.2-62.8)], for classic low-flux HD and high-flux hemodiafiltration, for bodily pain [45 (26.9-66.9) and 55 (35.6-87.5)], and for role limitations due to emotional functioning [0 (0-33.3) and 33.3 (0-100)], respectively. The scores did not differ significantly between the two types of hemodiafiltration. Conclusions: Our study indicates that QoL differs significantly among patients receiving low-flux HD and high-flux hemodiafiltration, on total SF-36, bodily pain, and role limitations due to emotional functioning. Convective modalities may offer better QoL than diffusive HD.