INTRODUCTION: Gallstone ileus (GSI) is a rare complication of gallstone disease estimated to account for 1%–4% of all bowel obstructions. It is the result of gallstone impaction in the small bowel through a biliary-enteric fistula. Limited epidemiological data exists on the number of hospitalizations, demographic variations, cost of care, comorbidity measures, and outcomes for GSI. METHODS: We analyzed the National Inpatient Sample (NIS) database for all hospitalizations with GSI (ICD-9 code 560.31) as primary or secondary diagnosis during the period from 2001-2011. NIS is the largest all-payer inpatient care database in the United States, containing data on more than 7 million hospital stays. Its large sample size is ideal for developing national and regional estimates. Statistical significance of variation were determined using Cochran-Armitage trend test. RESULTS: Between 2001 and 2011, number of hospitalizations for GSI increased from 1048 to 1255 (P < 0.0001, Figure 1A). GSI was found to be more common in women (P = 0.12) and Caucasians (P = 0.03). Although age group 65–79 remained the most commonly affected, age group 50-64 showed the greatest rise from 17.8% to 25.8% (P < 0.0001, Figure 1B). South remained the most commonly affected region (P = 0.22) throughout the study period. There was a significant rise in the West from 20.6% to 25.0% (P = 0.002) with a concurrent decrease in the Northeast from 24.2% to 20.3% (P = 0.04). A proportional decrease in the number of hospitalizations was seen at both, urban non-teaching (45.6% to 41.6%, P = 0.29, Figure 1C) and rural hospitals (19.9% to 9.9%, < 0.0001, Figure 1C), while the number increased at urban teaching hospitals (34.5% to 46.7%, P < 0.0001, Figure 1C). There was an overall increase in the cost of care from $17,285 to $23,739 (P < 0.0001, Figure 1D) whereas the mean length of stay ranged from 9.5 to 11.1 days (P = 0.28). Overall mortality ranged from 4.3% to 8.6% (P = 0.005). Some of the most commonly associated comorbid conditions with GSI were hypertension, fluid and electrolyte disorders, diabetes mellitus, anemia, and chronic pulmonary disease (Figure 2). CONCLUSION: A significant rise in the number of hospitalizations with GSI was found with interesting demographic variations and association with comorbidities. Although there was no significant change in their length of stay, there was a significant rise in the cost of care during the study period, perhaps due to increased use of newer, more advanced, diagnostic and treatment modalities.Figure 1Figure 2