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Timing of Antithrombotic Initiation and Risk of Reocclusion After Mechanical Thrombectomy. BACKGROUND AND OBJECTIVES: Early recanalization is crucial to improving outcomes in patients with acute ischemic stroke. Despite successful recanalization from mechanical thrombectomy (MT), approximately 2% to 20% patients may experience reocclusion. The present study analyzes the impact of timing of antithrombotic initiation in predicting reocclusion among patients who underwent MT with successful recanalization. METHODS: This was a multicenter analysis of patients who underwent successful recanalization from MT at 5 participating institutions across North America between January 2018 and December 2024. Successful recanalization was defined as thrombolysis in cerebral infarction 2b or higher. Timing of anti-thrombotic medication (antiplatelets/anticoagulants) initiation after MT was categorized into 4 groups as not started, within 24 hours, 1 to 7 days or beyond 7 days. RESULTS: A total of 53 patients who developed reocclusion and 618 who did not experience reocclusion after achieving successful recanalization from MT were included. After adjusting for baseline demographics and procedural characteristics, patients who received antithrombotics within 24 hours of MT experienced 84% lower odds of reocclusion compared with those were not started on antithrombotics (odds ratio: 0.16, 95% CI: 0.07-0.37, P < .001). Similarly, patients who received antithrombotics within 7 days experienced 94% lower odds for reocclusion (odds ratio: 0.06, 95% CI: 0.02-0.16, P < .001). Initiating antithrombotics more than 7 days after MT was not associated with a lower risk of reocclusion compared with no antithrombotic therapy. CONCLUSION: Early initiation of antithrombotic therapy after MT is protective against reocclusion, with the greatest benefit seen when started within 1 to 7 days, followed by within 24 hours. Initiation beyond 7 days was not protective against developing reocclusion.