There is no agreement whether intravenous prophylactic antibiotics can reduce infected pancreatic necrosis and mortality in acute necrotizing pancreatitis (ANP). We performed a meta-analysis comparing intravenous antibiotics with placebo or no treatment in randomized controlled trials (RCTs). Databases including MEDLINE, EMBASE, the Cochrane controlled trials register, the Cochrane Library, and Science Citation Index were searched to find relevant trials. Outcome measures were infected necrosis and mortality. Seven trials involving 467 patients were included. Analysis suggested infected pancreatic necrosis rates were not significantly different (antibiotics 17.8%, controls 22.9%), RR 0.81 (95% CI 0.54-1.22). There was nonsignificantly decreased mortality with antibiotics (9.3%) versus controls (15.2%), RR 0.70 (95% CI 0.42-1.17). Subsequent subgroup analysis confirmed antibiotics were not statistically superior to controls in reduction of infected necrosis and mortality. Prophylactic antibiotics cannot reduce infected pancreatic necrosis and mortality in patients with ANP.