AbstractThere are controversial opinions on the use of regional citrate anticoagulation (RCA) continuous renal replacement therapy (CRRT) in hyperlactatemia patients with increased bleeding risk. Patients with hyperlactatemia and increased bleeding risk who accepted RCA or no‐anticoagulation CRRT in our center were retrospectively included. Eighty patients who underwent RCA‐CRRT and 47 patients received no‐anticoagulation CRRT were included. Filter lifespan was significantly longer in the RCA group than the no‐anticoagulation group (44.5 hours [2‐89] vs 24.5 hours [1.5‐70], P < .001). The adjusted results demonstrated that patients in the no‐anticoagulant group had significantly higher risk of filter failure (HR = 4.765, 95% CI 2.703‐8.4, P ＜ .001). Bleeding episodes occurred in 19 (24.1%) and 22 (46.8%) patients in the RCA and no‐anticoagulation group, respectively (P = .012). The overall citrate accumulation (CA) rate was 5% in the RCA group. Patient mortality was associated with the comorbidity of hypertension, increased serum lactate level, and increased SOFA score. After matching, the filter lifespan was significantly longer in the RCA group than the no‐anticoagulation group. With careful monitoring and timely adjustment, RCA most likely was safe and effective for CRRT in hyperlactatemia patients with increased bleeding risk.