Objective: To investigate the clinical efficacy of continuous regional arterial infusion (CRAI) combined with blood purification therapy in treatment of severe acute pancreatitis (SAP). Methods: A historical comparative analysis was performed in the clinical data of 23 SAP patients from January 2008 to January 2011 undergoing CRAI plus blood purification therapy (CRAI group) and 26 SAP patients from January 2003 to September 2010 receiving traditional treatment (traditional group). The alterations of the clinical parameters before and after treatment, and therapeutic efficacies between the two groups were compared. Results: All the observed pre-treatment clinical variables had no obvious differences between the two groups (all P>0.05). On the third and seventh day after treatment, the body temperature, heart rate, APACHE-II score, white blood cell count, and levels of alanine transaminase and creatinine significantly decreased and the oxygenation index and platelet count significantly increased in CRAI group compared with traditional group (P<0.05 or P<0.01). The length of time of abdominal pain and for distension resolution, bowel function recovery and hospital stay in CRAI group were all shorter than those in traditional group (all P<0.01). Furthermore, the incidence of complications, surgical conversion rate and mortality of CRAI group were all significantly lower than those of traditional group (P<0.05 or P<0.01). Conclusion: Combination of CRAI and blood purification can improve the cure rate and reduce the complications of SAP, so it is an effective modality of treatment for SAP.