Abstract: OBJECTIV To compare the effects of CT-guided puncture drainage and open drainage on treatment of severe acute pancreatitis (SAP) patients with secondary peripancreatic abscess. METHODS A total of 39 SAP patients with secondary peripancreatic abscess who were treated in hospitals from Jan 2008 to Jun 2016 were enrolled in the study and divided into the observation group with 20 cases and the control group with 19 cases according to the treatment method. The control group was treated with open drainage, while the observation group was treated with CT-guided puncture drainage. The clinical effects and related clinical indexes were observed and compared between the two groups after the treatment. RESULTS The rate of postoperative residual abscess of the observation group was significantly lower than that of the control group; the time of recovery of body temperature and length of hospital stay of the observation group were significantly shorter than those of the control group; the hospitalization cost of the observation group was significantly less than that of the control group (P<0.05). The levels of CRP and PCT of the two groups of patients were reduced more significantly after the treatment than before the treatment (P<0.05), which were reduced more significantly in the observation group than in the control group (P<0.05). The total effective rate of treatment was 85.0% in the observation group, 78.9% in the control group, and there was no significant difference. The incidence of complications was 20.0% in the observation group, significantly lower than 73.7% in the control group(P<0.05). CONCLUSION The CT-guide puncture drainage can achieve significant therapeutic effect on the SAP patients with secondary peripancreatic abscess, shorten the time of recovery and length of hospital stay, and reduce the incidence of complications, as well as the hospitalization cost, with the safety high, and it is worthy to be promoted in the hospital.