Objective: To evaluate the impact of optimizing a standardized anticoagulation management protocol on the operational quality of continuous renal replacement therapy (CRRT) and related clinical outcomes. Methods: This was a single-center retrospective quality improvement study. Adult patients who underwent CRRT for ≥24 hours in the Intensive Care Unit of Linfen People’s Hospital between 2023 and 2025 were included. According to the implementation stages of the optimized anticoagulation management protocol, patients were divided into three annual groups. The distribution of anticoagulation strategies, filter lifespan per session, incidence of unplanned circuit interruption, bleeding complications, and ICU length of stay were compared among the three groups. Results: A total of 289 patients were included. With the implementation of the standardized anticoagulation management protocol, the proportion of regional citrate anticoagulation increased from 45.5% in 2023 to 83.5% in 2025. Filter lifespan was significantly prolonged (45.3 ± 12.1 h vs 72.4 ± 11.6 h, P < 0.001), while the incidence of unplanned circuit interruption and bleeding complications decreased over time (both P < 0.05). ICU length of stay also showed a downward trend (P = 0.009). Conclusion: The establishment and implementation of a CRRT-centered standardized anticoagulation management protocol were associated with prolonged filter lifespan, reduced complication rates, and improved operational quality of CRRT. This management approach may enhance the safety of blood purification therapy in critically ill patients in the ICU.