Background: Both cortical and cortical-subcortical (cortex-involved) lesions are typically associated with embolic stroke, of which atrial fibrillation (AF) is the common cause. The aim of this study was to find out the associations between cortex-involved stroke, vascular risk factors, and the subtypes (discovery time and duration) of AF. Methods: This was an imaging study of the China Atrial Fibrillation Screening in Acute Ischemic Stroke Patients (CRIST) trial. Between October 2013 and June 2015, 1511 acute ischemic stroke or transient ischemic attack (TIA) patients within 7 days after stroke onset at 20 Chinese hospitals were enrolled in this prospective, multicenter cohort, cross-sectional study. The final analysis of this sub-study included 243 patients with AF with required magnetic resonance imaging (MRI) sequences. AF was diagnosed by 6-day Holter monitoring and classified by duration of 24 h. Two stroke specialists blinded to the clinical information reviewed MRI (diffusion-weighted MRI). The third stroke specialists, also blinded to the clinical information, assessed the conflicts. Adjusted large artery atherosclerosis as confounding factor, the associations between cortex-involved lesions, vascular risk factors, and the subtype of AF were evaluated by univariate and multivariate regression analyses. Results: Of 243 acute ischemic stroke patients with AF, 190 were known AF and 53 were newly detected AF. There were 28 patients with AF persistent >24 h and 25 persistent ≤24 h in newly detected AF. Patients with newly detected AF were likely to have a fewer history of stroke or TIA (16.98% vs. 36.31%, P = 0.008) and lower fasting blood glucose (5.91 ± 1.83 mmol/L vs. 6.75 ± 3.83 mmol/L, P = 0.030) than patients with known AF. Among these 243 patients, 102 (41.98%) patients were with cortex-involved lesions. Cortex-involved lesions were significantly related to newly detected AF persistent >24 h (odds ratio [OR]: 4.517, 95% confidence interval [CI]: 1.490-13.696, P = 0.008), proteinuria (OR: 3.431, 95% CI: 1.530-7.692, P = 0.021), and glycosylated hemoglobin (OR: 0.632, 95% CI: 0.464-0.861, P = 0.004).Conclusions:Compared to previously known AF, newly detected AF persistent >24 h was associated with cortex-involved ischemic stroke. Copyright © 2019 The Chinese Medical Association.