Objective To assess predictive clinical factors of cardioembolic infarction in very old patients (85 years of age and older). Methods Prospective hospital-based stroke registry ("The Sagrat Cor Hospital of Barcelona Stroke Registry") is an acute-care teaching hospital in Barcelona, Catalonia, Spain. From 956 first-ever cardioembolic stroke patients included in the stroke registry over a 24-year period, 639 were younger than 85 years of age and 317 were 85 years or older (mean age 88.9 years). Demographics, clinical characteristics, risk factors and early outcome were compared. Predictors of cardioembolic infarction in the oldest age group were assessed by multivariate analyses. Results In a logistic regression model based on demographics, risk factors, clinical features and complications, female gender (odds ratio [OR] = 1.74, 95% confidence interval [CI]: 1.27–2.39), heart failure (OR = 2.27, 95% CI: 1.46–3.56), altered consciousness (OR = 1.76, 95% CI: 1.28–2.42), and infectious complications (OR = 2.01, 95% CI: 1.39–2.91) were predictors of cardioembolic stroke in the oldest age group. By contrast, heavy smoking, heart valve disease, hypertension, headache, early seizures, sensory deficit, and involvement of the posterior cerebral artery were independently associated with cardioembolic stroke in the younger group. Conclusions Identification of a differential clinical profile of cardioembolic stroke between patients aged 85 years or more and those younger than 85 years helps clinicians to the optimal management of ischemic infarction in the oldest segment of the population.