Objective To analyze the effects of prophylactic antibiotics on the patients with severe acute pancreatitis (SAP). Methods A total of 139 patients with SAP at Department of Critical Care Medicine, Ruijin Hospital from October 2011 to October 2016 were selected. Forty-eight patients using carbapenem antibiotics were included in this retrospective study after patients with infection of SAP at admission were excluded. Carbapenems were used prophylactically in two groups which included 34 cases in the group used antibiotics within 72 hours onset and 14 cases in the group used after 72 hours onset. The relationship between the time using antibiotic during 72 hours of SAP onset or after 72 hours and prognosis of pancreatic infection in patients with SAP was analyzed. Results There were no statistical differences in mortality at ICU, incidences of both pancreatic infection and extrapancreatic infections, duration of organ failure, and the length of ICU stays between two groups. It was indicated by univariate analysis that the higher incidence of pancreatic infection in patients with early prophylactic antibiotic treatment was related to the higher severity of disease including APACHE Ⅱ score, SOFA score and the higher degree of pancreatic lesions as CT severity index indicated. It was not related to gender, age, and the etiology of pancreatitis. However, there was no factor affected the failure of early prophylactic antibiotic treatment（carbapenem） identified by multivariate analysis. Conclusions It was not shown in this study early prophylactic antibiotic treatment within 72 hours onset can reduce ICU mortality, the incidence of pancreatic infection, and the length of ICU stays in the patients with SAP. For patients with higher severity and higher severe pancreatic lesions, individualized treatment protocols need to be developed.