Abstract Background and Aims Patients on hemodialysis (HD) experience a wide range of symptoms during and between dialysis that negatively affect their well-being. Addressing these symptoms, particularly from the patient's perspective, is a crucial component in the treatment. Our findings suggest a beneficial effect of hemodiafiltration (HDF) over hemodialysis (HD) on mortality and quality of life. This study aimed to investigate the differences in symptom severity between patients on HD and HDF. Method Patient-reported outcomes data of 1264 hemodialysis patients were extracted from CONVINCE, an international randomized controlled trial comparing high-dose hemodiafiltration with high-flux hemodialysis, including baseline and quarterly follow-up data up to 24 months. Symptoms were assessed using the CONVINCE peridialytic symptoms questionnaire covering inter- as well as intradialytic symptoms (see Table 1) with items scored between 0-100, higher scores indicating fewer symptoms. Prevalence and scores of all inter- and intradialytic symptom items at baseline and during follow-up visits were assessed and compared between HD and HDF groups. The association of changes of symptom scores over time with dialysis modality (HD vs. HDF) was assessed by Mixed Models for Repeated Measures (MMRM). Results MMRM analyses showed no significant main effects of dialysis modality on symptoms at the p <.05 level. However, descriptive statistics and plots indicated higher scores for most symptoms in the HDF group. The highest score differences between HDF and HD group over all timepoints were found for itchy skin (2.09 [95% CI −0.09-4.26]), numbness in hands or feet (2.03 [95% CI −0.22-4.28]), being washed out or drained (1.88 [95% CI −0.23-3.99]) and lack of appetite (1.73 [95% CI −0.03-3.50]). Plots for these symptoms can be found in Fig. 1. Furthermore, no significant interactions were found between dialysis modality and time, indicating that the rate of change in symptom scores did not differ significantly between the HDF and HD group. Conclusion No statistically significant differences in patient-reported symptoms between HDF and HD patients were found. We may not have the granularity of data to fully explore factors which may have contributed to the positive effects of HDF that have been reported previously. This might be due to the method of symptom assessment used or specific issues with perception of symptom burden. Our results highlight the complexity of symptom management in dialysis patients and underscore the need for future symptom assessments to allow for personalized treatment strategies that further optimize patient care.