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Background: It is not settled whether aspirin (ASA) failure may be predicted in stroke and transient ischemic attack (TIA) patients. The risk of ASA failure may be predicted by analyzing the epidemiological traits of patients with stroke or TIA., Patients and Methods: We evaluated retrospectively 695 stroke or TIA patients admitted to the Downtown Barcelona Stroke Registry, including 54 patients who recurred while on 125-500 mg/day of ASA (group ASA failure), and 178 patients who showed a good clinical response to the same dose of ASA for at least one year of follow-up (group ASA sensitive). Vascular risk factors, stroke subtypes, and clinical and radiological findings were compared in both groups., Results: On multivariate analysis ASA failure was independently correlated with history of myocardial infarction, nonvalvular atrial fibrillation or hypercholesterolemia. A trend toward age older than 65 was also correlated with ASA failure. On the contrary, periventricular lucencies were a protector factor. Stroke severity at clinical onset and at follow-up was unrelated to the intake of ASA at stroke onset., Conclusions: Males or females older than 65 years, with a history of coronary heart disease or atrial fibrillation, serum cholesterol level > 240 mg/dl, and a CT scan showing no evidence of small vessel disease are, respectively, the characteristics most frequently encountered in patients who suffer an ischemic stroke despite preventive treatment with 125-500 mg/day of ASA. Moreover, this treatment does not reduce initial and long-term stroke severity.