Objective: To investigate anticoagulation effects of nafamostat mesylate(NM) in sustained low-efficiency dialysis (SLED) and its relevant factors. Methods: Critically ill patients with kidney disease who were admitted to Zhongshan Hospital Affiliated to Fudan University and underwent SLED treatment from May to August 2024 were retrospectively included. Baseline clinical data were collected, and the activated partial thromboplastin time (APTT) and activated clotting time (ACT) were measured at the arterial end, before the filter, and at the venous end two hours post-NM anticoagulation treatment. Patients were categorized into two groups: the anticoagulation achievement group and the anticoagulation non-achievement group, based on the observed clotting status of the filter and venous reservoir following treatment completion. Multivariate logistic regression analysis was employed to identify risk factors influencing the efficacy of NM anticoagulation. Additionally, the receiver operating characteristic (ROC) curve was utilized to ascertain optimal monitoring indicators for NM anticoagulation. Results: A total of 96 patients (64 males and 32 females) aged (60±18) years undergoing SLED were included in the study, with 75 patients in the anticoagulation achievement group and 21 patients in the anticoagulation non-achievement group. No statistically significant differences were observed in baseline characteristics such as age, gender, body weight, baseline liver and kidney function, and platelet count between the two groups (all P>0.05). The proportion of patients with a baseline hematocrit (HCT)>30% was higher in the anticoagulation non-achievement group than that in the achievement group [57.1% (12/21) vs 22.7% (17/75), P=0.009]. The proportion of patients with fibrinogen (Fib)>4 g/L was also higher in the anticoagulation non-achievement group [90.5% (19/21) vs 49.3% (37/75), P<0.001]. The ultrafiltration rate in the anticoagulation achievement group was lower than that in the non-achievement group [232 (182, 353) ml/h vs 478 (289, 691) ml/h, P<0.001], and the NM dose was higher in the achievement group [35 (30, 40) mg/h vs 30 (25, 35) mg/h, P<0.001]. Multivariate logistic regression analysis revealed that high ultrafiltration rate (OR=1.489, 95%CI: 1.007-2.145, P<0.001), HCT>30% (OR=6.907, 95%CI: 1.523-18.342, P=0.009), and low albumin level (OR=0.821, 95%CI: 0.709-0.951, P=0.002) were relevant factors for poor NM efficacy. After 2 hours of NM treatment, the ratio of ACT at the venous/baseline ACT and the ratio of APTT at the venous/baseline APTT in the anticoagulation achievement group were both higher than those in the non-achievement group (both P<0.05). There was a positive correlation between APTT and ACT measured at the venous end 2 hours after NM treatment (r=0.763, P<0.001). The ROC curve analysis results showed that the area under the curve (AUC) for determining the effectiveness of NM anticoagulation using the ratio of APTT at the venous end to baseline APTT at 2 hours was 0.845 (95%CI: 0.762-0.928, P<0.001), with a cut-off value of 1.78 (sensitivity: 89.8%; specificity: 68.6%). Conclusions: Higher filtration rate, HCT>30% and lower albumin levels are identified as relevant factors for poor NM efficacy. Additionally, the ratio of venous/baseline APTT at 2 h after NM treatment may serve as a predictive indicator for assessing of NM anticoagulation.