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Introduction: Stroke mortality has decreased from 4th to 5th leading cause of death in the U.S. However, it is still a leading cause of disability and the disease burden associated with stroke by age is not well known.Methods: The study population consisted of 2003-2012 adult hospitalizations from the National Inpatient Sample of the Healthcare Cost and Utilization Project. Acute ischemic stroke (AIS) hospitalizations were identified by the principal diagnosis ICD-9-CM code. We estimated national acute ischemic stroke hospitalization rates and associated inflation-adjusted hospital costs across five consecutive 2-year time intervals (2003-04 through 2011-12), stratified by six age groups: 18-34 years, 35-44 years, 45-54 years, 55-64 years, 65-74 years, and ≥75 years.Results: The hospitalization rates per 100,000 persons with a principal diagnosis of AIS increased significantly among persons aged 18 to 54 years, but decreased significantly among those aged≥65 years. The largest increase was observed among ages 35-44 years. The average per-hospitalization cost increased 7%-19% across all 6 age groups after adjusting for inflation and the estimated total national cost increased 18% for AIS from 2003-04 to 2011-12. The estimated total cost for AIS hospitalization reached $12.55 billion in 2011-12.Conclusions: While AIS hospitalizations among ages ≥65 declined from 2003 to 2012, the hospitalization rates increased significantly among ages 18-54. The estimated hospital costs increased across all age groups during the study period, indicating the rising economic burden of stroke in the health care system.