【Abstract】Objective To investigate the effect of two different dilution modes during continuous venovenous hemodiafiltration (CVVHDF). Method Twenty patients who received CVVHDF with PRISMAFLEX V8.0 machine in West China Hospital were randomly assigned to pre- and post-dilution or total post-dilution, and then crossed over with each other. The life span of extracorporeal circuit and other performance metrics were compared between the two groups. Result During the treatment, there were no statistically significant differences in the changes of coagulation function indicators (t=0.654, P=0.521). There was no statistically significant difference in the frequency of blood pump suspension caused by alarm of venous pressure (t=0.539, P=0.232) and arterial pressure (t=0.705, P=0.415) per hour between the two groups. The average service life of extracorporeal circulation pipeline in the post-dilution treatment mode was 28.80±16.85 h, which was shorter than 40.25±20.32 h in the post-dilution treatment mode, and the difference was statistically significant (t=3.712, P=0.001). There were no statistically significant differences in the clearance efficiency of creatinine (t=-0.669, P=0.512) and urea (t=0.030, P=0.977) between the two groups. Conclusion Compared with post-dilution mode, pre- and post-dilution can effectively prolong the life-span of extracorporeal circuit during CVVHDF, and should be recommended in clinical practice.