Background: Because of a high risk of recurrence of ischemic events, some patients may be candidates for readministration of intravenous (IV) alteplase. Methods: We performed a single-center review and performed a search on PubMed from January 1966 to April 2014 for cases of readministration of alteplase. Favorable outcome was defined by a modified Rankin scale of 0 to 2 at discharge or at 1 to 3 months, improvement of greater than or equal to 4 points within 24 hours in the National Institutes of Health Stroke Scale score, or as a major improvement in the 72-hour National Institutes of Health Stroke Scale score. Results: Four ischemic stroke patients underwent readministration of IV alteplase in our single-center review. None of the patients had symptomatic or asymptomatic intracerebral hemorrhage. In 2 patients, IV alteplase had been administered for a previous acute ischemic stroke, 6 and 49 days before the index ischemic stroke. At discharge, both patients had a favorable outcome. A total of 22 cases of readministration of alteplase for ischemic stroke have been reported in literature. The mean interval between the 2 administrations of alteplase was 428 days (range, 3 hours to 2280 days). Asymptomatic postthrombolytic intracerebral hemorrhages were seen in 2 patients. Favorable outcome was seen in 16 patients. A total of 9 underwent readministration of IV alteplase within 3 months for recurrent ischemic stroke. Favorable outcome was seen in 5 of these 9 patients. Conclusions: We observed a relatively high rate of favorable outcomes and a small rate of adverse events after readministration of IV alteplase in ischemic stroke patients.