BACKGROUND: Unrecognized or silent myocardial infarction (MI) detected on an ECG is associated with first-ever stroke, but the impact on stroke recurrence is unknown. We aimed to determine the association of silent MI with stroke recurrence in patients with a recent ischemic stroke. METHODS AND RESULTS: Subjects from the IRIS (Insulin Resistance Intervention After Stroke) trial with an available ECG were included. Clinical MI was defined as a history of hospitalization for MI. Silent MI was defined as ECG evidence of MI in the absence of clinical MI. The primary outcome was recurrent stroke. Ischemic stroke and subtype were assessed as secondary outcomes. Multivariable Cox regression analysis adjusted for demographics, pioglitazone, and vascular risk factors was used to examine the association between MI and stroke recurrence. A total of 2282 participants met the inclusion criteria. Clinical and silent MI were identified in 161 (7.1%) and 94 (4.1%) subjects, respectively. Over the study period, 209 recurrent strokes occurred, with 191 classified as ischemic. In the fully adjusted model, silent MI was significantly associated with any stroke (hazard ratio [HR], 2.29 [95% CI, 1.34-3.90]) and ischemic stroke (HR, 2.09 [95% CI, 1.18-3.70]) recurrence. Clinical MI was associated with stroke recurrence in the unadjusted analysis but not in the fully adjusted model (HR, 1.31 [95% CI, 0.81-2.11]). Silent MI was not associated with potential cardioembolic subtypes (HR, 1.50 [95% CI, 0.70-3.22]). CONCLUSIONS: Among patients with a recent ischemic stroke, silent MI was associated with stroke recurrence. Tailored prevention strategies in this population warrant future investigation. REGISTRATION: URL: https://clinicaltrials.gov. Unique Identifier: NCT00091949.