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Background: Acute myocardial infarction (MI) has long been reported as a risk factor for ischemic stroke, but the magnitude and duration of risk remains uncertain.Methods: We performed a crossover-cohort study using inpatient and outpatient claims data from a nationally representative 5% sample of Medicare beneficiaries from 2008 through 2014. We identified all patients ≥66 years of age with a first-recorded hospitalization for acute MI. The primary outcome was ischemic stroke. All predictors and outcomes were defined using previously validated ICD-9-CM codes. To exclude stroke that may have been due to percutaneous coronary intervention, we included only cases of ischemic stroke that occurred after discharge from the MI hospitalization. We compared the risk of ischemic stroke in successive 4-week periods during the 12 weeks after MI versus the corresponding 4-week periods 1 year later. To avoid immortal time bias, we limited our cohort to patients who remained alive and insured throughout the 15 month study period. Odds ratios (OR) and absolute risk differences were calculated using the Mantel-Haenszel estimator for matched data.Results: We identified 22,798 patients with an acute MI in whom the mean age was 77.4 (±7.9) years and 50.3% were women. In the 12 weeks after discharge, 216 patients (0.95%) developed a stroke, as compared to 21 (0.09%) patients in the corresponding 12-week period 1 year later. The absolute increase in stroke risk was 0.45% (95% confidence interval [CI], 0.36-0.55%) in the first 4 weeks after acute MI compared to the 4-week time period 1 year later, corresponding to an OR of 18.2 (95% CI, 8.1-50.6). The absolute risk increase was 0.24% (95% CI, 0.16-0.31%) during weeks 5-8 (OR, 8.7; 95% CI, 4.0-22.6) and 0.17% (95% CI, 0.10-0.23%) during weeks 9-12 (OR, 5.8; 95% CI, 2.7-14.1).Conclusions: Acute MI is associated with a substantially elevated short-term risk of ischemic stroke. This risk was independent of periprocedural stroke risk in the setting of coronary reperfusion therapies.