Abstract: OBJECTIVE To investigate the effect of early enteral nutrition (EN) on intestinal flora and late phase infection in patients with severe acute pancreatitis (SAP). METHODS 85 SAP patients were continuously collected from Feb. 2015 to Dec. 2017, and were randomly divided into the study group (42 cases) and the control group (43 cases). The study group were treated with early EN, and the control group received total parenteral nutrition (TPN). The nutritional status, intestinal mucosal damage degree, intestinal flora and prognosis were compared between the two groups. RESULTS Serum albumin in the study group was significantly higher than that in the control group on the 14th day after hospital admission, and the study group showed significantly higher serum prealbumin than the control group on the 7th day and 14th day (P<0.05). From the 7th day on, the study group showed significantly lower serum endotoxin, D-lactic acid and DAO than the control group (all P<0.05). The study group showed significantly higher amounts of Bifidobacterium and Lactobacillus from the 7th day (P<0.05). The study group had significantly lower amounts of Clostridium difficile and Enterobacter and Enterococcus, whereas significantly higher amount of Bacteroidetes (P<0.05) than the control group on the 14th day. In terms of clinical prognosis, the study group showed significantly lower incidence of IPN, ARDS and sepsis, in addition, with shorter length of ICU stay and hospital stay than the control group (P<0.05). CONCLUSION Early EN can effectively improve the nutritional status, reduce the degree of intestinal mucosal damage, regulate the imbalance of intestinal flora, reduce the incidence of IPN, and improve the prognosis in SAP patients.