Objective To observe the clinical efficacy of coupled plasma filtration adsorption (CPFA) combined with high volume hemofiltration (HVHF) for severe acute pancreatitis (SAP) and explore the practicality, the safety and the therapeutic mechanism. Methods This was a prospective, randomized clinical trail. A total of 29 patients with SAP were di-vided into two groups:treatment group (n=15, CPFA and HVHF) and control group (n=14, HVHF). The APACHEⅡscore, se-rum triglyceride, liver and kidney function, white blood cell (WBC), heart rate (HR), respiration, mean arterial pressure (MAP) and oxygenation index were compared before and after treatment between two groups. The organ function was as-sessed, and the adverse reactions and prognosis were observed in two groups. Results After treatment, there were signifi-cant decreases in APACHEⅡscore and WBC, and significant increase in PaO2/FiO2 in two groups, especially significant in treatment group. There was a significant decrease in the level of triglycerides in 7-d treatment group than that of 3-d treat-ment group (P＜0.05). There were no thrombocytopenia, bleeding, allergies, blood clotting and other adverse reactions in two groups of patients. There were significant decreases in the blood purification time and the length of hospital stay in treatment group than those of control group (P＜0.05). There was no significant difference in mortality between two groups. Conclu-sion CPFA combined with HVHF can effectively control inflammation, reduce the serum level of triglyceride and improve the prognosis in patients with SAP.