Objective To investigate the difference of anticoagulant efficacy of heparin and citric acid during continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis, and analyze their effects of on filter life span, length of hospital stay and mortality. Methods Patients with severe acute pancreatitis in Intensive Care Unit of the First Affiliated Hospital of Hebei North University between January 2018 and July 2022 were retrospectively enrolled, and they were divided into heparin group (control group) and citric acid group (research group) according to anticoagulation methods. The differences of anticoagulant catheter blockage during CRRT, filter life span, length of hospital stay, and 90-day mortality between the two groups were analyzed. Results A total of 108 patients were enrolled, including 56 in the research group and 52 in the control group. In pre-CRRT treatment, the balance value of fluid intake and outflow in the research group was significantly lower than that in the control group (P<0.05). The 108 patients received 217 times of CRRT treatment totally, with a median length of treatment of 63 h (range 44-87 h). The severity of catheter blockage in the research group was lower than that in the control group (P=0.003). The filter life span was longer in the research group than that in the control group [42.5 vs. 29.0 h; hazard ratio=1.83, 95% confidence interval (1.23, 2.73), P<0.001]; in the comparison of 90-day mortality, there was no significant difference between the two groups (P>0.05). The mean use of filters in the research group was less than that in the control group (1.93±0.09 vs. 2.17±0.14, P<0.001). The downtime of CRRT due to filter life in the research group was obviously shorter than that in the control group [120 (0, 720) vs. 300 (0, 890) min, P=0.029], while the duration of CRRT in the research group was remarkably better than that in the control group [10.6 (4.9, 27.7) vs. 8.1 (3.6, 25.0) d, P=0.024], and the risk of filter replacement due to special conditons in the research group was lower than that in the control group (46.4% vs. 65.4%, P=0.048). There was no statistically significant difference in the length of intensive care unit hospitalization or total hospitalization between the two groups (P>0.05). Conclusion Both heparin and citric acid could assist the treatment of CRRT, while citric acid might be apt to improve local coagulation and systemic inflammatory response.