OBJECTIVES: The use of effective but high cost interventions and improved survival may affect the cost of a hospital admission. Thus, hospital costs for AIS may be expected to increase more than the average cost of medical care, as measured by the CPI, as the mix of cases change. The purpose of the study was to compare the actual trends in costs and charges for hospital admissions for AIS with the CPI, both overall and by use of tPA and mechanical thrombectomy (MT). METHODS: A total of 499,661 hospital admissions for AIS were extracted from the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP) data for 2005-2010. Cost per admission was estimated from total charges using each hospital’s cost-to-charge ratio and were compared with CPI trends in changes in health care costs provided by the US Bureau of Labor and Statistics. Use of tPA and/or MT was examined using multiple regression analyses. RESULTS: Cost of an acute care admission for AIS increased at a greater rate, annually, than the CPI from 2005 through 2008, but appeared to level of in 2009, with tPA admission most closely following the CPI. Utilization of tPA increased in 2005 from 1.84% to 5.47% in 2010. The number of admissions with MT increased from 0.87% to 8.09% over the same time period. Charges for AIS admissions have increased much more rapidly than the CPI observed from 2005 to 2010, with admissions receiving tPA having the greatest gain in charges. CONCLUSIONS: Cost of care for AIS patients who receive tPA follows the CPI trend, while costs for non-tPA patients increase at a greater rate. This disparity could indicate a widening gap between cost and reimbursement for non-tPA admissions, and/or a failure of many hospitals to accurately record the use of tPA for billing purposes.