The incidence of acute pancreatitis (AP) is increasing. Twenty percent of AP patients with developing necrotizing pancreatitis (NP), while ~40-70% of NP patients develop potentially fatal infectious complications. When patients are suspected or confirmed infected pancreatic necrosis (IPN), antibiotics should be administered timeously to control the infection, but long-term use of antibiotics can lead to multidrug-resistant bacteria (MDRB) infection and eventually to increased mortality. Our study aimed to determine the incidence of MDRB infection and evaluate the risk factors for MDRB infection in IPN patients.Clinical data of IPN patients admitted to the general surgery department of Xuanwu Hospital of Capital Medical University between January 1, 2014, and December 31, 2021, were retrospectively analyzed.IPN patients (n = 267) were assigned to MDRB infection (n = 124) and non-MDRB infection (n = 143) groups. On admission, patients in the MDRB group had a higher modified computer tomography severity index (CTSI) score (P < 0.05), pancreatic necrosis degree, and PCT level (P < 0.05) than those in the non-MDRB group, and the prognosis of patients in MDRB group was poor. The most common gram-negative bacteria were Acinetobacter baumannii (n = 117), the most common gram-positive bacteria were Enterococcus faecium (n = 98), and the most common fungal infection was Candida albicans (n = 47). Multivariable analysis showed that complications of EPI (OR: 4.116, 95% CI: 1.381-12.271, P = 0.011), procalcitonin (PCT) level at admission (OR: 2.728, 95% CI: 1.502-4.954, P = 0.001), and degree of pancreatic necrosis (OR: 2.741, 95% CI: 1.109-6.775, P = 0.029) were independent risk factors for MDRB infection in IPN patients.We identified common infectious strains and risk factors for MDRB infection in IPN patients.© 2022 Lu et al.