BACKGROUND: Although cystic fibrosis (CF) is widely considered a lung disease, the prevalence of CF-specific gastrointestinal symptoms and diseases has continued to rise. Peptic ulcer disease (PUD) has not been well-studied among people with CF (PwCF) and may be a common cause of abdominal symptoms. In PwCF, impaired bicarbonate secretion and unbuffered gastric acid production have been attributed to the development of ulcers, although ulcers remain uncommon. The objective of this study was to evaluate the prevalence of PUD in PwCF and assess for possible contributing factors. METHODS: This study utilized the National Inpatient Sample (NIS) database. All patients 18 years or older with CF were identified from 2014 to 2019. Relevant patient characteristics and procedures were identified using ICD-9 and ICD-10 codes. Linear trend, bivariate analyses, and multiple regression analysis were performed. The outcomes of interest were peptic ulcer disease, pancreatic insufficiency, and nonalcoholic steatohepatitis or NASH. All analyses accounted for complex sampling scheme of the NIS. RESULTS: The total prevalence of PwCF in the National Inpatient Sample (NIS) database was 0.08 %, and the number was stable year to year from 2014 to 2019. Hispanic patients were more likely to be diagnosed with PUD than other white (aOR 1.802 [1.311,2.476]). Multiple regression analysis indicated that PUD in PwCF was strongly associated with a diagnosis of NASH (aOR 2.421[1.197, 4.898]). PUD patients were less likely to have pancreatic insufficiency compared to the non-PUD group (aOR 0.583 [0.455, 0.745]). CONCLUSION: Although cystic fibrosis has been historically known as a disease of childhood, advancements in therapy have led to prolonged life expectancy and higher prevalence for cystic fibrosis-related digestive diseases. This study revealed a low prevalence of PUD in PwCF. Hispanics and those with NASH are more likely to develop peptic ulcers.