BACKGROUND The safety of intravenous thrombolysis (IVT) in patients with acute ischemic stroke over the age of 80 is unclear. We hypothesized that patients over the age of 80 can be safely treated with IVT. METHODS Admission and discharge data were collected on all patients at a single tertiary care center presenting within 12 hours of onset. Collected data included treatment with IVT, demographics, pretreatment National Institutes of Health Stroke Scale score, length of stay, mortality, and discharge disposition. Analyses were restricted to patients over the age of 80, and the primary outcome was in-hospital mortality. Logistic regression was used to examine whether IVT was associated with mortality. RESULTS Between January 1, 2005 and May 30, 2010, 112 patients over the age of 80 presented within 3 hours of ischemic stroke onset, and 31 received IVT. There were 15 deaths. In multivariable models adjusted for age, sex, race-ethnicity, and National Institutes of Health Stroke Scale, treatment with IVT, compared with no treatment, was not associated with in-hospital death (adjusted odds ratio, 1.2; 95% confidence interval, 0.3-4.3). CONCLUSIONS Treating ischemic stroke patients over 80 years with IVT was not associated with an increase in mortality in an urban tertiary care center.