〔Abstract〕 Objective To analyze the risk factors of nosocomial infection in patients with severe acute pancreatitis (SAP) and explore its nursing countermeasures. Methods A retrospective analysis of 75 patients with acute SAP admitted to Henan Hongli Hospital from January 2018 to August 2020 was conducted to investigate the clinical data of the patients, record the occurrence of nosocomial infection, analyze the risk factors of nosocomial infection, and formulate targeted nursing interventions. Results Infection occurred in 10 of 75 patients (13.33 %). All were respiratory tract infections. Multivariate logistic regression analysis showed that diabetes mellitus, mechanical ventilation, deep vein catheterization, abdominal drainage tube indentation, indentation catheter, organ failure number, long fasting time and high modified computed tomography severity index (MCTSI) score were all independent risk factors for nosocomial infection in SAP patients (P < 0.05). ConclusionThe incidence of nosocomial infection in SAP patients is high, diabetes, multiple iatrogenic invasive operations, long fasting time, and high MCTSI score are closely related to the occurrence of nosocomial infection in patients. In clinical practice, the protection of patients should be strengthened to avoid infection occurs.