Objective To compare the efficacy in patients with severe pancreatitis treated by minimally invasive surgery and open surgery. Methods Seventy-three cases of patients with severe pancreatitis which were treated in our hospital between June 2011 and June 2015 were divided into group A (n = 37) and group B(n =36). Group A were treated by minimally invasive surgery while group B by open surgery. The perioperative stress reactions , postoperative inflammatory reactions , incidence of complications and mortality were compared between the two groups. Results The proportion of patients with perioperative (0+1) level pain in group A (70.3%) was significantly higher than that in group B (44.4%) (P < 0.05). Seventy-two hours after surgery, the CRP, TNF-α and IL-6 in group A were lower than those before surgery and those in group B while APN in group A was higher than that before surgery and that in group B (P < 0.05). The incidence of pulmonary infection and mortality in group A (27.0%, 5.4%) were lower than those in group B (50.0%, 22.2%) (P < 0.05). Conclusions Minimally invasive surgery in the treatment of severe pancreatitis has slight trauma. The postoperative pain is mild and complications are fewer , and the mortality is low.