Background and Purpose-Some studies suggest that taking aspirin regularly at the time of the onset of stroke reduces stroke severity. Other studies suggest the converse (ie, that previous aspirin therapy is associated with greater stroke severity). We sought to examine this question among the patients enrolled in the International Stroke Trial (IST). Methods-Analysis of the associations of reported use of aspirin in the 3 days before randomization in IST with baseline stroke severity (as assessed by stroke clinical syndrome, predicted outcome at 6 months, and observed outcome at 6 months). We adjusted analyses for confounding factors. Results-We excluded those patients who were first scanned after trial entry and were found to have an intracerebral hemorrhage as the cause of the stroke leading to randomization. We performed analyses for all treatment groups combined. For the 17 850 patients with ischemic stroke, data at baseline and follow-up were available for 100% and 99%, respectively. Among these patients, 3820 (21.4%) reported previous aspirin use. Previous aspirin use appeared, in univariate analyses, to be associated with greater baseline stroke severity, more severe stroke syndrome, and, in control subjects, worse observed outcome at 6 months. However, after adjustment, these associations were no longer significant. Conclusions-In this large prospective and complete data set, we found no evidence of any association of previous aspirin use with baseline stroke severity. The analyses suggest that previously reported positive and negative associations may well have been attributable to the play of chance in small samples, confounding or other biases, rather than a biological effect of aspirin.