In patients with mild acute pancreatitis, the majority of patients do not require antibiotic prophylaxis for infection unless combined with biliary system infection, such as cholecystitis or cholangitis, because most patients have mild clinical symptoms and no significant impairment of major organ function. However, for patients with severe acute pancreatitis, the need for prophylactic antibiotics is still inconclusive, and although numerous studies have been reported, the conclusions obtained are widely divergent due to the different conditions of the patients observed in these studies and the different antibiotics used, and some studies have even reached completely opposite conclusions. In recent years, some scholars have adopted the internationally recognized evidence-based medicine approach and critically evaluated the results of all studies, which showed that the prophylactic application of antibiotics in the early stage of severe acute pancreatitis does not significantly reduce late secondary infections and mortality, but also may cause bacterial resistance, secondary fungal infections and increase the economic burden, etc. Therefore, we do not recommend the prophylactic application of antibiotics for all patients with severe acute pancreatitis. Therefore, we do not recommend the prophylactic application of antibiotics for all patients with severe acute pancreatitis. However, for patients with large pancreatic necrosis (>30%) or combined with other systemic failure, empirical prophylactic antibiotics can be considered, but preferably for no longer than 2 weeks.