BACKGROUND: Ileus is a well-known complication of acute pancreatitis (AP). There are limited data on the factors associated with ileus, as well as its impact on AP patients. We aimed to investigate the incidence and clinical predictors of ileus in hospitalized AP patients. METHODS: We queried the 2016-2019 National Inpatient Sample (NIS) database using the International Classification of Diseases (ICD)-10 codes. Adult patients diagnosed with AP (ICD-10 K85) were included, excluding those with chronic pancreatitis. Demographics, comorbidities, complications and interventions were stratified by the presence of ileus. Multivariate analysis identified factors associated with ileus, adjusting for patient and hospital characteristics, comorbidities, and pancreatitis complications. RESULTS: Among 1,386,390 AP patients, 50,170 (3.6%) developed ileus. Female sex was associated with a lower risk (adjusted odds ratio [aOR] 0.56, 95% confidence interval [CI] 0.53-0.58; P<0.001). Hispanic patients had the lowest risk (aOR 0.82, 95%CI 0.76-0.88), while older age groups had a higher risk. Pseudocysts (P<0.001), sepsis (P<0.001) and portal vein thrombosis (P<0.001) were significant predictors. Pancreatic drainage was associated with ileus (P=0.007), but endoscopic retrograde cholangiopancreatography was not. Patients with ileus had greater mortality (P<0.001), longer hospital stays (+4.9 days, P<0.001), and higher costs ($67,855.91, P<0.001). CONCLUSIONS: This study highlights age, sex and racial disparities in the development of ileus in patients with AP. It also reveals a significant association of ileus with pseudocysts, portal vein thrombosis, and pancreatic drainage. Early recognition and timely enteral feeding are crucial to prevent disease progression and improve outcomes.