Objective: To investigate the distribution and antimicrobial resistance of pathogens isolated from infections associated with acute necrotizing pancreatitis (ANP) and analyze their impacts on prognosis of the patients. Methods: The clinical data of 72 ANP patients complicated with infection admitted from October 2010 to October 2014 were retrospectively studied. Results: Of the 72 ANP patients, there were 47 cases (65.28%) with abdominal and retroperitoneal infection, 37 cases (51.39%) with respiratory infection, and 32 cases (44.44%) with bloodstream infection, and bloodstream infection was closely related to death of the patients (P<0.05). Of 235 pathogenic isolates, 159 (67.66%) were gram-negative bacteria, 60 (25.53%) were gram-positive bacteria and 16 (6.81%) were fungi, respectively. The top six common pathogens isolated were Acinetobacter baumanni (58 isolates, 24.68%), Pseudomonas aeruginosa (21 isolates, 8.94%), Klebsiella pneumonia (19 isolates, 8.09%), Enterococcus faecium/faecalis (19 isolates, 8.09%), Escherichia coli (18 isolates, 7.66%) and Staphylococcus aureus (11 isolates, 4.68%), respectively. Antimicrobial susceptibility testing indicated that the resistant rate for Acinetobacter baumanni and Pseudomonas aeruginosa to imipeniem was 95.92% and 52.63%, and to cefperazone-sulbactam was 59.26% and 50.00%, respectively. The detection rate of extended-spectrum β-lactamases (ESBLs) in Klebsiella pneumonia and Escherichia coli was 64.29% and 80.00%, respectively. The resistance rate of Klebsiella pneumonia and Escherichia coli to cefperazone-sulbactam was 31.58% and 18.75%, and to imipeniem was 23.08% and 7.14%, respectively. Of the 19 isolates of Enterococcus faecium/faecalis, there was only one isolate resistant to vancomycin, and no linezolid-resistant isolate was found. The detection rate of Methicilin-resistant Staphylococcus aureus was 72.73%, and no isolate resistant to vancomycin, linezolid or macrodantin was noted. None of the 16 isolates was found resistant to common antifungal drugs. Conclusion: Bloodstream infection is an important cause for death in ANP patients. The gram-negative bacteria are still the major pathogens causing infections in ANP patients, however, the proportion of gram-positive bacteria and fungi should not be neglected. Multi-drug resistant bacteria have become an increasing challenge to the treatment of ANP associated with infections.