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INTRODUCTION: While incident ischemic lesions (IILs) are not unusual on follow-up magnetic resonance imaging (MRI) following stroke, their risk factors and prognostic significance remain unknown.METHODS: In a prospective multicenter study of 503 acute stroke patients, we assessed IILs on registered MRI images at baseline and 6 months, analyzing risk factors and clinical outcomes across 36 months.RESULTS: At 6 months, 78 patients (15.5%) had IILs, mostly diffusion-weighted imaging-positive (72%) and clinically covert (91%). Older age and small vessel disease (SVD) lesions were baseline risk factors for IILs. IILs were associated with worse cognitive (beta for global cognition: -0.31, 95% confidence interval [CI]: -0.48 to -0.14) and functional outcomes (beta for modified Rankin scale [mRS]: 0.36, 95% CI: 0.14 to 0.58), and higher recurrent stroke risk (hazard ratio: 3.81, 95% CI: 1.35 to 10.69). IILs partially explained the relationship between SVD and poor cognition.DISCUSSION: IILs are common and are associated with worse cognitive and functional outcomes and stroke recurrence risk. Assessing IILs following stroke might aid prognostication.HIGHLIGHTS: Incident ischemic lesions (IILs) were assessed with registered baseline and 6-month magnetic resonance imaging (MRI) scans in a stroke cohort. IILs 6 months after stroke are present in one-sixth of patients and are mostly clinically silent. Small vessel disease burden is the main baseline risk factor for IILs. IILs are associated with cognitive and functional impairment and stroke recurrence. Assessing IILs by follow-up MRI aids long-term prognostication for stroke patients.