Although age is a major risk factor for stroke, physicians are often reluctant to use thrombolytic agents in those who are very old. No published study provides detailed information on the use of intravenous tissue plasminogen activator (tPA) in patients aged 90 years or older. We retrospectively reviewed the use of intravenous tPA for patients 90 years or older who were admitted with acute ischemic stroke to the hospital at 4 academic centers from March 1, 1999, to March 1, 2008. We reviewed the clinical features of the patients at presentation, complications, and outcomes. Twenty-two patients (11 women; median age, 93 years; range, 90-101 years) were identified who had received intravenous tPA for symptoms of acute ischemic stroke (average time to treatment, 143 minutes; range, 90-180 minutes; no tPA protocol violations; mean National Institutes of Health Stroke Scale score, 15; range, 5-28). Nearly all patients were highly functional at baseline (median modified Rankin Scale [mRS] score, 1; median Barthel Index score, 95), and all but one performed the activities of daily living with little or no assistance before stroke. By the 30-day follow-up, 2 patients (9%) had a favorable outcome (mRS score, 0-2) and 2 (9%) had moderate disability (mRS score, 3). Most patients died (n=10) or experienced severe disability, defined as an mRS score of 4 or 5 (n=5). Asymptomatic intracerebral hemorrhage occurred in 3 patients (14%) and was nonfatal. Most patients aged 90 years or older who received intravenous tPA for acute ischemic stroke had poor 30-day functional outcomes or died. Intravenous tPA treatment in this age group does not improve the outcome of ischemic stroke.