Recent evidence of pancreatic penetration of several antibiotics active against the usual flora found in pancreatic sepsis, at therapeutic minimal inhibitory concentration, prompted the authors to perform a randomized, multicenter, clinical trial on imipenem prophylaxis in acute pancreatitis. Seventy-four patients with computed tomographic (CT) scans demonstrating necrotizing pancreatitis within 72 hours of onset were randomly assigned to two groups receiving no antibiotic treatment or 0.5 gram of prophylactic imipenem administered intravenously every eight hours for two weeks. Pancreatic sepsis was always detected by means of cultures (percutaneous CT or ultrasound-guided needle aspiration and intraoperative samples). The incidence of pancreatic sepsis was much less in treated patients (12.2 versus 30.3 percent, p < 0.01). Therefore, the authors recommend prophylactic use of imipenem in patients with acute necrotizing pancreatitis.