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Introduction: The duration of heightened stroke risk after acute myocardial infarction (MI) remains uncertain.Methods: We performed a retrospective cohort study using inpatient and outpatient claims data from 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries ≥66 years of age. Our exposure of acute MI and the outcome of ischemic stroke were ascertained using previously validated ICD-9-CM diagnosis codes. To exclude periprocedural strokes from percutaneous coronary intervention, we only included strokes occurring after discharge from acute MI hospitalization. Patients were censored at the time of ischemic stroke, death, end of Medicare coverage, or September 30, 2015. We fit Cox regression models separately for the groups with and without acute MI to examine its association with ischemic stroke after adjustment for demographics, stroke risk factors, and Charlson comorbidities. We used the corresponding survival probabilities to compute the hazard ratio (HR) in each 4-week interval after discharge. Confidence intervals (CI) were computed using the nonparametric bootstrap method.Results: Among 1,746,476 beneficiaries, 46,182 were hospitalized for acute MI and 80,466 for ischemic stroke. Compared to patients without acute MI, patients with acute MI were older (mean age 79.0 vs 73.1 years) and had more stroke risk factors. After adjustment for demographics, stroke risk factors, and Charlson comorbidities, the risk of ischemic stroke was highest in the first 4 weeks after discharge from the MI hospitalization (HR, 2.7; 95% CI, 2.3-3.2), remained substantially elevated during weeks 5-8 (HR, 2.0; 95% CI, 1.6-2.4) and weeks 9-12 (HR, 1.6; 95% CI, 1.3-2.0), and was no longer significantly elevated afterward (Figure).Conclusions: Acute MI is associated with a substantially elevated short-term risk of ischemic stroke which appears to extend beyond the 30-day period enshrined in current stroke etiological classification systems.