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We estimated the annual burden and costs of hospitalization in patients with chronic gastrointestinal and liver diseases, and identified characteristics of high-need, high-cost patients, in a nationally representative sample.Using Nationwide Readmissions Database 2013, we identified patients with at least 1 hospitalization between January and June 2013, and a diagnosis of inflammatory bowel diseases (IBDs), chronic liver diseases (CLDs), functional gastrointestinal disorders (FGIDs), gastrointestinal hemorrhage, or pancreatic diseases, with 6 months or more of follow up. We calculated days spent in hospital/month and estimated costs of the entire cohort, and identified characteristics of high-need, high-cost patients (top decile of days spent in hospital/month).Patients with IBD (n = 47,402), CLDs (n = 376,810), FGIDs (n = 351,583), gastrointestinal hemorrhage (n = 190,881), or pancreatic diseases (n = 98,432), hospitalized at least once, spent a median of 6 to 7 days (interquartile range, 3–14 d) in the hospital each year (total for all diseases). Compared to patients in the lowest decile (median, 0.13–0.14 d/mo spent in the hospital), patients in the highest decile spent a median 3.7–4.1 days/month in hospital (total for all diseases), with hospitalization costs ranging from $7502/month to $8925/month and 1 hospitalization every 2 months. Gastrointestinal diseases, infections, and cardiopulmonary causes were leading reasons for hospitalization of these patients. Based on multivariate logistic regression, high-need, high-cost patients were more likely to have Medicare/Medicaid insurance, lower income status, index hospitalization in a large rural hospital, high comorbidity burden, obesity, and infection-related hospitalization.In a nationwide database analysis of patients with IBD, CLD, FGID, gastrointestinal hemorrhage, or pancreatic diseases hospitalized at least once, we found that a small fraction of high-need, high-cost patients contribute disproportionately to hospitalization costs. Population health management directed toward these patients would facilitate high-value care.