BACKGROUND Phosphorus-containing dialysis solution is used to prevent hypophosphatemia in patients undergoing continuous venovenous hemodiafiltration (CVVHDF). This study evaluated the effect of phosphorus-containing dialysis solution on mortality in patients undergoing CVVHDF based on changes in phosphorus and red cell distribution width-coefficient of variation (RDW-CV) levels. METHODS We included 272 patients with acute kidney injury (AKI) who underwent CVVHDF at the medical intensive care unit from 2017 to 2019 and classified them according to Phoxilium (Baxter Healthcare Ltd.), as a phosphorus-containing dialysis solution, use within 48 hours after CVVHDF initiation. Clinical data were collected at baseline and 48 hours after CVVHDF initiation. The primary outcome was all-cause mortality during the follow-up period. RESULTS The non-Phoxilium (NP) group had higher phosphorus and lower RDW-CV levels than the Phoxilium (P) group (phosphorus, 7.3 ± 4.3 vs. 5.0 ± 2.8 mg/dL; RDW-CV, 14.6 ± 1.9 vs. 15.7 ± 2.6%; all p < 0.001). In the multivariable Cox proportional hazard regression of the NP group, an increase in phosphorus and RDW-CV at 48 hours of CVVHDF was associated with mortality (delta phosphorus: median, >0 mg/dL vs. <-2.0 mg/dL; hazard ratio [HR], 8.62; 95% confidence interval [CI], 2.10-35.32; p = 0.003/delta RDW-CV: median, >0% vs. <-0.2%; HR, 4.34; 95% CI, 1.49-13.18; p = 0.008). Meanwhile, in the P group, an increase in delta RDW-CV was associated with mortality (delta RDW-CV: >0% vs. >-0.2% and <0%; HR, 2.65; 95% CI, 1.12-6.24; p = 0.03), while an increase in delta phosphorus was not. CONCLUSIONS In patients with AKI undergoing CVVHDF, the risk factors for all-cause mortality differed according to the initial phosphorus levels and use of Phoxilium.