Results of a previous randomized multicenter trial involving 102 patients with severe acute pancreatitis treated with or without adjuvant selective decontamination (SD) were analyzed additionally with regard to the bacteriologic status of (peri)pancreatic necrosis. The incidence of gram-negative pancreatic infection was significantly reduced in patients treated with SD (P = .004). Once such an infection develops, mortality increases 15-fold (P < .001) in comparison with that for patients with sterile necrosis. Among patients in whom only gram-positive infection of pancreatic necrosis was found, there was no significant increase in mortality. These results were similar in both treatment groups. In addition, the hospital stay was significantly longer in cases of gram-negative infected necrosis. The incidence of gram-positive infected necrosis in patients treated with SD did not increase. Gram-negative pancreatic infection can be prevented with adjuvant SD, thereby reducing mortality among patients with severe acute pancreatitis.