Background: The occurrence of infectious complications characterizes the more severe forms of acute pancreatitis (AP) and is associated with high mortality. We investigated the effects of infection at different sites in patients with AP, including those with necrotizing pancreatitis (NP). Methods: We conducted a retrospective analysis of 285 patients who met the inclusion criteria for AP and were admitted to Tianjin Nankai Hospital between January 2016 and September 2019. According to the source of the culture positivity during hospitalization, patients were divided into four groups: sterile group(n = 148), pancreatic infection group(n = 65), extrapancreatic infection group(n = 22) and combined infection group(n = 50). The source of infection, microbiology, biochemical parameters and prognostic indicators were analyzed. Results: In terms of baseline characteristics, the four groups were similar in age, sex, aetiology, previous pancreatitis and diabetes. Compared with the severity of the disease in the other groups, the APACHE II scores(9.91 ± 4.65, 9.46 ± 5.05, respectively) and organ failure rate (40.9 and 50%, respectively)were higher in the extrapancreatic infection group and the combined infection group (P < 0.05). The frequency of surgical intervention and hospitalization time in patients with NP complicated with extrapancreatic infection was greatly increased (P < 0.05). Regarding the primary outcome, patients in the combined infection group had longer hospital stays (68.28 ± 51.80 vs 55.58 ± 36.24, P < 0.05) and higher mortality (24.0% vs 9.2%, P < 0.05) than patients in the pancreatic infection group. In addition, patients in the extrapancreatic infection group also showed high intensive care utilization (59.1%) and mortality rates (18.2%). Among the 137 AP patients with infection complications, 89 patients exhibited multidrug-resistant (MDR) microorganisms, and the mortality rate of patients with MDR bacterial infection was higher than that of patients with non-MDR bacterial infection (24.7% vs 3.6%, P = 0.001). Conclusion: Clinicians should be aware that extrapancreatic infection (EPI) significantly aggravates the main outcome in pancreatic infection patients. Infection with MDR bacteria is also associated with AP mortality.