OBJECTIVES: Better selection of ischemic stroke patients for intravenous recombinant tissue plasminogen activator (IV tPA) treatment based on the penumbral hypothesis as seen through magnetic resonance imaging (MRI) by may improve clinical outcomes. However given the limited availability of MRIs in hospitals, MRI-based methods may not be feasible.  We examined the cost-effectiveness of adding perfusion imaging with computed tomography (CTP) to usual computed tomography (CT)-based methods to examine presence and extent of penumbra such that patients can be identified for IV tPA treatment. METHODS: A decision-analytic model was developed to estimate costs and outcomes associated with selecting patients for IV tPA treatment via CTP compared to current usual care of selection based on CT scan and patient history from a hospital perspective. The patient population was similar to that observed in the IV tPA clinical trials included in a recent meta-analysis. Clinical data was derived from published clinical trials. Costs were obtained from standard US costing sources and utilities were obtained from published literature. All costs are presented in 2009 US dollars. Outcomes included cost per life-year saved and cost per quality-adjusted life-year (QALY) gained. Sensitivity analyses were conducted. RESULTS: From the hospital perspective, the addition of penumbral-based CTP selection improved favorable outcome (modified Rankin Scale ≤ 1) by 0.59% and reduced cost by $42 compared with usual CT-based selection at hospital discharge. Life years and QALYs improved which resulted in the addition of penumbral-based CTP selection in being cost-savings to hospitals. Multivariate sensitivity analysis predicted cost-effectiveness (≤ $50,000 per QALY) in 89.2% of simulation runs. CONCLUSIONS: Given costs and the limited availability of MRI, penumbral-based CTP after routine CT is a cost effective alternative for hospitals in selecting ischemic stroke patients for IV tPA treatment.