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Mechanical thrombectomy has the potential to improve recanalization rates and outcomes for patients with ischemic stroke, but potential gains could be offset by procedural complications and costs. We evaluated the cost and utility of combined intravenous (IV) tissue-type plasminogen activator (tPA) and mechanical thrombectomy compared to IV tPA alone for acute large-vessel ischemic stroke.We constructed a decision tree for a hypothetical 68-year-old with a large-vessel ischemic stroke who is eligible for IV tPA. The interventional strategy was IV tPA, a cerebral angiogram, and mechanical thrombectomy and thrombolysis if indicated. Recanalization, hemorrhage complications, and outcomes for the interventional strategy were from the Multi-MERCI study. The medical strategy was IV tPA using inputs from a comprehensive systematic review. Costs were estimated from Medicare reimbursements. We modeled lifetime costs and utilities for disability using a Markov model and Monte-Carlo multivariable sensitivity analysis.For the baseline scenario, the recanalization rate was 72.9% for the interventional strategy and 46.2% for the medical strategy. For the interventional strategy, the symptomatic hemorrhage rate was 8.6% with recanalization and 15.4% without. For the medical strategy, the corresponding rates were 3.6% and 13.3%, respectively. The interventional strategy was cost-effective in 97.6% of simulations (incremental cost-effectiveness ratio $16 001/quality-adjusted life year; 95% CI, $2736–$39 232).Based on observational data, the combination of IV tPA and mechanical thrombectomy for large-vessel ischemic stroke appears to be cost-effective compared to IV tPA alone. These findings require additional validation with randomized trial data.