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Introduction There is clinical equipoise behind bridging intravenous thrombolysis (BT) with endovascular thrombectomy (EVT). We performed a cost‐effectiveness analysis comparing EVT and BT versus EVT alone. Methods We conducted a model‐based cost‐utility analysis comparing the cost‐effectiveness of EVT alone vs. EVT and BT for patients with acute ischemic stroke. We used a decision tree to examine the short‐term costs and outcomes at 90 days after the index stroke. Subsequently, we developed a Markov state transition model to assess the costs and outcomes over 1‐year, 5‐year, and 20‐year time horizons. Treatment costs were based on administrative data. Clinical outcome inputs were derived from literature included in our systematic review. We considered the impact of disability and recurrent stroke on mortality risk, health‐related quality of life, and costs. We estimated total and incremental cost, quality‐adjusted life years (QALYs), and incremental cost‐effectiveness ratio (ICER), expressed as an incremental cost per QALY gained of EVT and BT compared with EVT alone.Probabilistic analysis was used to calculate the reference case estimates. Results The average costs per patient were estimated to be $55,503, $57,814, $68,183, and $84,946 for EVT only strategy, and $47,311, $49,556, $59,625, and $75,898 for EVT and BT over 90‐day, 1‐year, 5‐year, and 20‐year, respectively. The cost saving of EVT only strategy was driven by the avoided medication costs of IVT (ranging from $8,193 to $9,048). The additional thrombolytics led to slight decrease in QALY estimate during the 90‐day time horizon (loss of 0.0016 QALY), but a small gain over 1‐year, 5‐year, and 20‐year time horizons (0.0108, 0.0638, and 0.1481 QALY). With similar outcomes and less cost, the EVT only strategy was cost‐effective compared with EVT and BT. Analyses with longer time horizon show lower probabilities of EVT only strategy being cost‐effective. At a fixed willingness to pay threshold of $50,000, the probabilities of EVT only to be cost‐effective were 100%, 100%, 99.0%, and 65.9% over 90‐day, 1‐year, 5‐year, and 20‐year time horizons. At the willingness to pay thresholds of $100,000 per QALY, the probabilities of EVT only strategy being cost‐effective was 22.8% over the 20‐year time horizon. Conclusions Our cost‐effectiveness model suggested that bridging with thrombolytics may not be cost‐effective for patients with acute ischemic stroke secondary to large vessel occlusion.