Background and Purpose— The aim of this study was to assess the costs and cost-effectiveness of intravenous thrombolysis treatment with alteplase (Actilyse) of acute ischemic stroke with 24-hour in-house neurology coverage and use of magnetic resonance imaging. Methods— A health economic model was designed to calculate the marginal cost-effectiveness ratios for time spans of 1, 2, 3 and 30 years. Effect data were extracted from a meta-analysis of six large-scale randomized and placebo-controlled studies of thrombolytic therapy with alteplase. Cost data were extracted from thrombolysis treatment at Aarhus Hospital, Denmark, and from previously published literature. Results— The calculated cost-effectiveness ratio after the first year was $55 591 US per quality-adjusted life-year (base case). After the second year, computation of the cost-effectiveness ratio showed that thrombolysis was cost-effective. The long-term computations (30 years) showed that thrombolysis was a dominant strategy compared with conservative treatment given the model premises. Conclusions— A high-quality thrombolysis treatment with 24-hour in-house neurology coverage and magnetic resonance imaging might not be cost-effective in the short term compared with conservative treatment. In the long term, there are potentially large-scale health economic cost savings.