β2-Microglobulin (β2-MG) and α1-microglobulin (α1-MG) have molecular weights of 11,800 and 33,000 Da, respectively. We studied the α1-MG and β2-MG reduction ratios (RRs) and survival in patients on predilution online haemodiafiltration (Pre-OL-HDF). Participants were 247 Pre-OL-HDF patients. α1-MG and β2-MG RRs were assessed at baseline. Kaplan-Meier survival and Cox proportional hazard analyses were used. In 247 patients, the median age was 67 (56-73) years, the dialysis duration was 77 (46-150) months, and the diabetes prevalence was 47.4%. Twenty-two patients died over the 450-day study period. The mortality cut-off values using receiver-operating characteristic curves for the α1-MG and β2-MG RRs were 20% and 80%, respectively. Survival rates were significantly (p < 0.05) higher in patients with α1-MG RRs ≥20% (n=134) compared with patients with α1-MG RRs <20% (n=113) and in patients with β2-MG RRs ≥80% (n=87) compared with patients with β2-MG RRs <80% (n=160). Cox models adjusting for diabetes and dialysis duration showed that α1-MG RR, β2-MG RR, and pre- and postdialysis β2-MG were risk factors for all-cause mortality; however, after additional adjustment for age, sex, and serum albumin, only β2-MG RR and pre- and postdialysis β2-MG were significant predictors of mortality (p < 0.05). α1-MG RRs were significantly correlated with β2-MG RRs (ρ=0.73, p < 0.0001) and serum albumin levels (ρ=0.13, p < 0.05). In patients on Pre-OL-HDF, α1-MG RRs ≥20% and β2-MG RRs ≥80% were associated with better survival, β2-MG RR ≥80% and pre-and postdialysis β2-MG levels were significant predictors of all-cause mortality, and α1-MG RR ≥20% may predict mortality.