Background and Purpose— Weekend admissions are associated with higher in-hospital mortality. However, limited information is available concerning the “weekend effect” on stroke mortality. Our aim was to evaluate the impact of weekend admissions on stroke mortality in different settings. Methods— We analyzed all hospital admissions for ischemic stroke from April 2003 to March 2004 through the Hospital Morbidity Database. The Hospital Morbidity Database is a national database that contains patient-level sociodemographic, diagnostic, procedural, and administrative information including all acute care facilities across Canada. The major inclusion criterion was admission to an acute care facility with a principal diagnosis of ischemic stroke. Clinical variables and facility characteristics were included in the analysis. Results— Overall, 26 676 patients were admitted to 606 hospitals for ischemic stroke. Weekend admissions comprised 6629 (24.8%) of all admissions. Seven-day stroke mortality was 7.6%. Weekend admissions were associated with a higher stroke mortality than weekday admissions (8.5% vs 7.4%; odds ratio, 1.17; 95% CI, 1.06 to 1.29). Mortality was similarly affected among patients admitted to rural versus urban hospitals or when the most responsible physician was a general practitioner versus specialist. In the multivariable analysis, weekend admissions were associated with higher early mortality (odds ratio, 1.14; 95% CI, 1.02 to 1.26) after adjusting for age, sex, comorbidities, and medical complications. Conclusions— Stroke patients admitted on weekends had a higher risk-adjusted mortality than did patients admitted on weekdays. Disparities in resources, expertise, and healthcare providers working during weekends may explain the observed differences in weekend mortality.