IntroductionPrevious randomized controlled trials (RCTs) and meta-analyses comparing Hemodiafiltration (HDF) with conventional hemodialysis (HD) on the effectiveness of HDF for mortality in end-stage renal disease (ESRD) patients have yielded contrasting results. Importantly, we sought to compile the available information to provide the most up-to-date and reliable evidence.MethodsWe systematically searched PubMed, Embase and Cochrane Library for RCTs up to January 14, 2024. Review Manager 5.3 software was used to analyze relevant data and evaluate the quality of evidence.ResultsOur study involved 10 randomized controlled trials with 4654 chronic dialysis patients. Compared to hemodialysis, hemodiafiltration demonstrated a reduction in all-cause mortality (relative risk [RR] 0.84, 95% confidence intervals [CI] 0.72–0.99, P = 0.04) and cardiovascular mortality (RR 0.74, 95% CI 0.61–0.90, P = 0.002). However, it did not reduce the rate of sudden death (RR 0.92, 95% CI 0.64–1.34, P = 0.68) and infection-related mortality (RR 0.70, 95% CI 0.47–1.03, P = 0.07). A subgroup analysis revealed that HDF demonstrated superiority over high-flux hemodialysis in terms of all-cause mortality, while not over low-flux hemodialysis (RR 0.81, 95% CI 0.69–0.96, P = 0.01; RR 0.93, 95% CI 0.77–1.12, P = 0.44, respectively). Furthermore, a subgroup analysis for convection volume found that hemodiafiltration with a convection volume of 22 L or more reduced all-cause and cardiovascular mortality (RR 0.76, 95% CI 0.65–0.88, P = 0.0002, RR 0.73, 95% CI 0.54–0.94, P = 0.01, respectively).ConclusionIn maintenance hemodialysis patients, hemodiafiltration can reduce mortality compared to conventional hemodialysis. Furthermore, this effect is more pronounced in HDF with high convection volume.