Background and Purpose-Thrombolytic therapy is licensed for use in highly selected patients with acute ischemic stroke. We aimed to model the health economic impact of limited use of thrombolytic therapy and to assess whether it was likely to be cost-effective when used more widely in the UK National Health Service (NHS). Methods-The authors formed a discussion panel to develop the decision-analysis model of acute stroke care. It consisted of Markov state-transition processes, with probabilities of different health states determined by certain key variables. The range of estimates of efficacy of recombinant tissue plasminogen activator (rt-PA) was taken from an update to a Cochrane systematic review of randomized trials of thrombolysis. Data on outcome after stroke were taken from our hospital-based stroke register, supplemented by data derived from relevant literature sources. Results-The model suggested that compared with standard care, if eligible patients were treated with rt-PA up to 6 hours, there was a 78% probability of a gain in quality-adjusted survival during the first year, at a cost of pound13581 per quality-adjusted life-year (QALY) gained. Over a lifetime, rt-PA was associated with cost-savings of pound96565 per QALY. However, the estimates were imprecise and highly susceptible to the assumptions used in the economic model; under several plausible assumptions, rt-PA was much less cost-effective than standard care, and under others, a great deal more cost-effective. Conclusions-The estimates of effectiveness and cost-effectiveness were imprecise. Although the benefits appeared promising, the data did not support the widespread use of thrombolytic therapy outside the terms of the current restricted license in routine clinical practice in the NHS. There is a case for new large-scale randomized trials comparing thrombolytic therapy with control up to 6 hours to determine more precisely the effects of rt-PA on short-term and long-term survival and its cost-effectiveness when used in a wider range of patients.