OBJECTIVES: Crohn’s disease (CD) is a chronic, inflammatory condition of the gastrointestinal tract with no curative therapy available. Past studies are either outdated or lack sufficient depth to provide a comprehensive picture of the burden of CD in the United States (US). This study aims to fill that gap. METHODS: Publicly available US databases (NIS, MEPS, NAMCS, NHAMCS) covering inpatient hospitalizations, outpatient hospitalizations, emergency department hospitalizations, and provider office visit settings were examined in terms of both raw usage to quantify resource utilization and via regression analysis to better understand drivers. Broader economic and healthcare utilization was analyzed from the Medical Expenditure Panel Survey. RESULTS: This study estimates that there roughly 600,300 individuals with CD in the US in 2010. The total economic burden of those with CD is almost $12.5billion, with direct medical expenditures accounting for ~$7.6 billion and indirect costs of ~4.8billion. The portions of these costs that are directly attributable to CD are~$3.8billion and ~$1.9billion, respectively. CONCLUSIONS: CD imposes a significant burden on the US healthcare system despite its relatively small prevalence. The findings here are in line with those elsewhere in the literature and underscore the potential savings from better disease management and care delivery. Given the economic burden outlined in this study, CD is an area that is ripe for increased investment and deserves more attention.