BACKGROUND: Diagonal earlobe crease has been shown as the association between atherosclerotic disease. AIM: To examine the relationship between diagonal earlobes crease (DELC) and ischemic stroke. METHODS: This prospective study recruited 175 consecutive acute ischemic stroke patients admitted to the Stroke Unit of Srinagarind Hospital, Faculty of Medicine, Khon Kaen University between May 2021 and August 2021. Clinical data included age, gender, underlying disease, clinical presentation, vital signs, brain computed tomography and DELC assessed for both ears.  The study was approved by the Human Ethics Research Committee of Khon Kaen University, Thailand. RESULTS: patients were assessed on clinical presentation and brain computed tomography (CT) findings. There were 31 patients with transient ischemic attacks (17.7% of the patients) and 144 patients with cerebral infarction (82.3%). In all participants were male 58.9% and 72 were female (41.1%). The top three clinical presentations were hemiparesis (29.6%), dysarthria (27.0%), and facial palsy (17.5%). One hundred and thirty-one patients (74.9%) had underlying diseases; hypertension (24.2%), diabetic mellitus (14.4%), atrial fibrillation (4.9%), chronic kidney disease (2.0%), dyslipidemia (8.0%), valvular heart disease (2.3%), coronary heart disease (2.6%), previous stroke (8.1%), and other diseases (8.4%). Only 44 patients (25.1%) had no underlying disease. Frank’s sign (DELC) was present in only 13 patients (7.4%). There were similar proportions of major underlying conditions, hypertension, and diabetic mellitus for both groups, and no differences apparent for gender or old age. On CT scans both DELC and non-DELC patients showed lacunar infarction as the major source of ischemic stroke.  CONCLUSIONS: Due to our very small sample of DELC patients, we could draw no conclusions about the relationship between DELC and ischemic stroke and its predictive utility as a biomarker for ischemic stroke.  Given the much higher proportions of DELC patients reported in international literature we raise the possibility of physiological, genetic, or ethnic differences in Thai, or Asian samples, for future research.