BACKGROUND AND PURPOSE: Hypercoagulable states are a rare but recognized cause of ischemic stroke. Evaluation for these coagulation disorders is costly, but establishing a diagnosis may lead to a change in treatment. We estimated the incremental cost of specialized coagulation testing per additional ischemic stroke patient placed on a regimen of warfarin therapy. METHODS: The cost-effectiveness analysis was performed based on data from a consecutive series of 674 adult ischemic stroke patients admitted to an academic medical center over a 3-year period. Those with atrial fibrillation or warfarin contraindications were excluded. Specialized coagulation test costs (protein C, protein S, antithrombin III, plasminogen, activated protein C resistance/factor V Leiden mutation, lupus anticoagulant, and anticardiolipin antibodies) were based on Medicare reimbursement rates. Effectiveness was defined as the difference in proportions of patients tested for coagulation disorders (coagulopathy present, normal complete battery, or incomplete) and treated with warfarin versus those patients who were not tested and treated with warfarin (the comparator). The incremental cost-effectiveness ratio (ICER) was defined as the cost associated with changing 1 patient to warfarin therapy. RESULTS: The base case ICER was $1,102 per additional patient treated with warfarin. The only factor that led to a significant change in the ICER was the proportion of untested patients treated with warfarin. The results of 2-way sensitivity analyses revealed a minimum ICER of $496 and a maximum ICER of $2,959. CONCLUSIONS: Strategies optimizing the selection of patients for specialized coagulation testing are needed. Outcomes-based cost-effectiveness cannot be determined until the impact of secondary prevention with anticoagulation in patients with specific coagulopathies is known.