Abstract： Objective： To observe the clinical efficacy of different hemodialysis modalities in the treatment of elderly patients with end-stage renal disease （ESRD）. Methods：A total of 50 ESRD patients undergoing hemodialysis at the outpatient department of Zhumadian Central Hospital from March 2022 to June 2023 were selected. After a four-week washout period， the patients sequentially underwent conventional hemodialysis （HD）， high-flux hemodialysis （HFHD）， and hemodiafiltration （HDF） once each， with a two-week interval between each modality. Levels of small molecule toxins [serum creatinine （SCr）， blood urea nitrogen （BUN）， and serum phosphorus （P）]， middle and large molecule toxins [β2-microglobulin （ β2-MG）]，albumin（ Alb），and C-reactive protein（ CRP）] were compared before and after each dialysis session. Results：Before dialysis，there were no significant differences in the levels of SCr，BUN，P，β2-MG，Alb，and CRP among the three dialysis modalities（ P＞0.05）. After dialysis，SCr， BUN，P，and β2-MG levels were significantly reduced compared with those before dialysis （P＜0.05）. The SCr levels were lower in HD and HDF compared to those in HFHD，and BUN levels were lower in HDF compared to those in HD and HFHD （P＜0.05）. There were no significant differences in P levels among the three dialysis modalities （P＞0.05）. The Alb levels were increased significantly after all three dialysis modalities （P＜0.05）. The HD resulted in lower Alb levels compared to HFHD and HDF，and higher β2-MG levels compared to HFHD and HDF；HDF had lower β2-MG levels compared to HFHD， with all differences being significant （P＜0.05）. There were no significant differences in CRP levels before and after dialysis or among the three dialysis modalities （P＞0.05）. Conclusion： All three hemodialysis modalities can effectively remove small molecule toxins in treating elderly ESRD. HFHD is superior to HD in removing β2-MG，while HDF has the best clearance effect and can more significantly improve nutritional status.