Objective To evaluate the efficacy of multiple minimally invasive therapy and individualized treatments combination in severe acute pancreatitis. Methods The data of sixty-seven patients with severe acute pancreatitis between September 1998 and October 2008 undergoing multiple minimally invasive therapy and individualized treatments were analyzed retrospectively. The changes of APACHE Ⅱ score, CT score, WBC count, total bilirubin, AST, blood glucose, amylase, lypase, C-reactive protein, tumor necrosis factor-α, blood urea nitrogen, creatinine, and oxygenation index (PaO2/FiO2) were observed and compared between before and after treatment. Time of abdominal pain relieved, laparotomy rate, mortality rate, recovery rate, hospital stay, and cost of hospitalization were also observed. Results All the detected indexes improved significantly after treatments compared with those before treatments （Plt;0.001）. Time of abdominal pain relieved was (20.17±14.16) h. Laparotomy rate was 6.0% （4/67）. Mortality rate was 7.5% （5/67）. Recovery rate was 92.5% （62/67）. Hospital stay was (30.85±28.37) d and cost of hospitalization was (59 295.78±34 564.44) yuan. Conclusions Multiple minimally invasive therapy and individualized treatments for cases of severe acute pancreatitis with different causes, course, severity of disease, and complications, could significantly improve the clinical indexes and recovery rate of severe acute pancreatitis.