Objective To explore and summarize the application of minimally invasive technique to every stage of severe acute pancreatitis (SAP). Methods The treatment of 101 SAP patients admitted to our hospital between January 1995 and December 2008 were retrospectively analyzed. After calculi were removed by endoscopic retrograde cholangiopancreatograpy (ERCP) and endoscopic sphincterotomy (EST), endoscopic nasobiliary drainage (ENBD) were applied, then rhubarb liquid was perfused into gut with a nutrient canal and ultrasound-guided abdominal drainage tube were simultaneously placed at the early stage. Some patients received continuous renal replacement therapy (CRRT) at the same time. Laparoscopic cholecystectomy (LC) was performed at the subacute stage, and choledochoscope was introduced to remove parapancreatic necrotic tissues at the late stage of SAP.Results Of all the 101 cases treated by the method mentioned above, 75 cases received ERCP (or EST) and ENBD, and 31 cases underwent rhubarb liquid perfusion with a nutrient canal. Eight cases underwent continuous renal replacement therapy (CRRT). Forty-eight cases underwent LC and ultrasoundguided abdominal drainage. Thirtysix cases with infected peripancreatic tissue or abscess underwent debridement under choledochoscope 3 to 14 times at the later stage. Five cases died of multiple organ failure (MOF) and acute respiratory distress syndrome (ARDS). The hemobilia ocurred in 2 patients during choledochoscopy and was cured under direct visualization by electric coagulation. Intestinal fistula happened in 3 cases and cured by drainage. Pancreatic pseudocyst was latterly seen in 3 cases and treated by the anastomosis of cyst with jejunum through selective operation. After the hospitalization of 9-132 d (mean 24 d), 96 cases completely recovered. Conclusion Timely application of minimally invasive technique to every stage of SAP can avoid the defects of traditional operations, decrease the injury and interference to the maximum, and raise the cure rate.