Background Troponin elevation with electrocardiography changes is not uncommon in patients with acute ischemic stroke; however, it is still unclear whether the mechanism of these changes is due to cardiac problems or neurally mediated myocytic damage. Thus, we investigated cardiac and neurological predictors of troponin elevation in those patients. Methods and Results We retrospectively analyzed medical data of the prospectively registered ischemic stroke patients on stroke registry who were admitted and underwent a serum cardiac troponin I and 12‐lead electrocardiography within 24 hours of symptom onset. However, patients with well‐known troponin‐elevating comorbidities were excluded from the analysis. Among 1404 ischemic stroke patients, 121 (8.7%) had elevated troponin, which was defined as more than 0.04 mg/mL. Multivariable analysis identified electrocardiography abnormalities such as QT c‐prolongation (odds ratio [ OR ]: 1.52, 95% CI : 1.02–2.28), left ventricular hypertrophy ( OR : 2.14, 95% CI 1.43–3.19), Q‐wave ( OR : 2.53, 95% CI : 1.48–4.32), and ST elevation ( OR : 2.74, 95% CI : 1.12–6.72) as cardiac variables associated with troponin elevation, and higher National Institutes of Health Stroke Scale score ( OR : 1.04, 95% CI : 1.01–1.07) and insular cortical lesions ( OR : 2.78, 95% CI : 1.85–4.19) as neurological variables associated with troponin elevation. Incidence of troponin elevation as well as QT c‐prolongation was increased further in combination with cardiac and neurological factors. Conclusions Certain cardiac and neurological conditions in acute ischemic stroke may contribute to troponin elevation. The proposed concept of cardiac vulnerability to cerebrogenic stress can be a practical interpretation of troponin elevation and electrocardiography abnormalities in stroke patients.