Background and Purpose-This study describes the large variations in outcome after stroke between countries that participated in the International Stroke Trial and seeks to define whether they could be explained by variations in case mix or by other factors. Methods-We analyzed data from the 15 116 patients recruited in Argentina, Australia, Italy, the Netherlands, Norway, Poland, Sweden, Switzerland, and the United Kingdom, We compared crude case fatality and the proportion of patients dead or dependent at 6 months; we used logistic regression to adjust for age, sex, atrial fibrillation, systolic blood pressure, level of consciousness, and number of neurological deficits, We used the frequency of prerandomization head CT scan and prescription of aspirin at discharge to indicate quality of care, Results-The differences in outcome (all treatment groups combined) between the “best” and “worst” countries were very large for death (171 cases per 1000 patients) and for death or dependency (375 cases per 1000 patients). The differences were somewhat smaller after adjustment for case mix (160 and 311 cases per 1000 patients, respectively), Process of care may have accounted for some but not all of the residual variation in outcome. Conclusions-Adjustment for case mix explained only some of the variation in outcome between countries. The residual differences in outcome were too large to be explained by variations in care and most likely reflect differences in unmeasured baseline factors. These findings demonstrate the need to achieve balance of treatment and control within each country in multinational randomized controlled stroke trials and the need for caution in the interpretation of nonrandomized comparisons of outcome after stroke between countries.