Background: Cystic fibrosis (CF), the most prevalent genetic disorder among persons of European decent, is an autosomal recessive disorder due to CFTR gene mutations which lead to abnormally viscid exocrine secretions of the pancreas and other exocrine glands of the body. Exocrine pancreatic insufficiency (EPI) is a condition seen in ~85% of CF patients, in which the pancreas is unable to secrete adequate amounts of digestive enzymes. Although most patients with CF develop EPI, not all cases of EPI are caused by CF. Other risk factors for EPI include acute or chronic pancreatitis which may be triggered by alcohol, among other etiologies. Some studies suggest alcohol use as a possible independent risk factor for development of various cancers. Given these associations, we sought to characterize the prevalence of both alcohol use and cancer in patients with EPI vs patients with CF. Methods: A retrospective observational study was performed using electronic health records in Ochsner System, Louisiana, over a 3 year period: January 2017 to January 2020. Two cohorts were reviewed: patients with EPI excluding CF (n=596) and patients with CF (n=81). Results: While there was no significant difference in the prevalence of cancer at start vs end of the 3 year observation period in the CF cohort (4.1% at start, 7.2% at end), the prevalence of cancer was significantly greater among patients in the EPI cohort, both at start and end of the 3 year period: 15.95% at start, 43.9% at end (p <0.05). Also, while there was no significant change in alcohol use over the 3 year period for the CF cohort, the prevalence of alcohol use was significantly lower in CF cohort (0.45% at start, 2.2% at end) compared to EPI cohort which showed significant increase in alcohol use over the observation period: 7.7% at start vs 16% at end (p <0.05). Conclusions: There was a significantly higher prevalence of cancer in the EPI cohort compared to the CF cohort; while this may be due to higher prevalence of pancreatic cancer associated with EPI compared to CF, it does not explain the entirety of this observation. Not only was there a significantly higher prevalence of alcohol use in EPI cohort compared to CF cohort, but over the 3 year observation there was a 2-fold increase in prevalence of alcohol use within patients who already had a diagnosis of EPI. Within the EPI cohort, the observed increase in cancer prevalence and the increase in alcohol warrant further investigation into which factors unique to EPI patients without CF may modulate these social and health risk indices.