Introduction: Correct adjustment of dry weight after hemodialysis (HD) with no signs of hypervolemia is important. Intradialytic hypotension (IDH) is the most common complication during HD. IDH occurs in 15% to 30% and possibly in up to 50% of dialysis sessions. IDH augments mortality essentially due to chronic overhydration and the inability to reach the proper dry weight. On-line hemodiafiltration (ol-HDF) has been reported to reduce the frequency of IDH. The aim of this study was to assess the effect of ol-HDF on hemodynamic stability and dry weight adjustment compared with low-flux HD. Methods: IDH-prone HD patients at our center were enrolled. This study was designed as a crossover trial with two phases (A arm: low-flux HD for 8 weeks followed by ol-HDF for 8 weeks vs. B arm: ol-HDF for 8 weeks followed by low-flux HD for 8 weeks) and two treatment arms (ol-HDF vs. low-flux HD), each phase lasting 8 weeks. We measured the proportion of body water using a body composition monitor (BCM). Results: In a comparison of the systolic blood pressure (SBP) and diastolic blood pressure (DBP) reductions from the baseline blood pressure between the HD and ol-HDF groups, statistically significant differences were observed only in the SBP of the B arm (SBP: HD vs. HDF, -9.83 ± 6.64 vs. -4.62 ± 1.61 mmHg, p = 0.036; DBP: HD vs. HDF, -3.29 ± 4.05 vs. -1.86 ± 1.49 mmHg, p = 0.261). Neither the mean of the interdialytic body weight gains nor the frequency of IDH was different between the A and B arms (p = 0.817 and p = 0.562, respectively). In terms of dialysis modality, there were no significant differences in the amount of overhydration between the conventional HD and ol-HDF groups during the two study phases, as measured by the BCM (A arm: p = 0.875, B arm: p = 0.655). Conclusion: Our study did not show a better benefit of ol-HDF to reach the dry weight compared with low-flux HD in IDH-prone patients.