OBJECTIVES: To estimate the cost-effectiveness of intravenous recombinant tissue plasminogen activator (rt-PA) therapy for acute ischemic stroke from the perspective of Taiwan National Health Insurance system. METHODS: A decision-analytic model was developed to perform the cost-effectiveness analysis of rt-PA treatment for acute ischemic stroke. We considered only costs of hospitalization (initial acute care and recurrence) because estimates of long-term care in Taiwan are not available. The estimates of efficacy of rt-PA were based on an updated Cochrane systematic review of randomized trials of thrombolysis. Data on costs, health outcomes, and utilities of disability were taken from a hospital-based study (360 first-ever ischemic stroke patients), national statistics, and literature-derived values. Costs per quality-adjusted life-year (QALY) were calculated for a hypothetical cohort of 1000 eligible patients, with starting age 65 years. RESULTS: The model suggested that over the lifetime a patient treated with rt-PA (within 3 hours of stroke onset) gained 0.21 QALYs, at a cost of NT$131,900 (US$4,211) per QALY. CONCLUSIONS: Using rt-PA in treating acute ischemic stroke in Taiwan is likely to generate health benefits at modest extra costs.