BACKGROUND: In 2008, the European Cooperative Acute Stroke Study-3 (ECASS-3) demonstrated that intravenous-tissue plasminogen activator could be safely administered for acute stroke patients presenting between 3 and 4.5 hours from symptom onset. Recently, the Food and Drug Administration rejected expansion of this time window in the United States. We sought to determine how many fewer patients would be treated by maintaining this restricted time window. METHODS: We reviewed charts from patients who received intravenous thrombolysis at the University of Alabama at Birmingham between January 2009 and December 2011. Patients were divided into two groups (treated within 3 hours of onset, treated between 3 and 4.5 hours from onset). Demographics, stroke severity and protocol deviations according to the ECASS-3 trial were collected. Our safety measures were any hemorrhagic transformation, symptomatic intracerebral hemorrhage and systemic hemorrhage. RESULTS: Two hundred and twelve patients were identified, of whom 192 were included in our analysis. A total of 36 patients (19%) were treated between 3 and 4.5 hours. No statistical differences were seen between age (p=0.633), gender (p=0.677), race (p=0.207) or admission stroke severity (p=0.737). Protocol deviations from the ECASS-3 criteria were found in 20 patients (56%). These were primarily age > 80 and aggressive blood pressure management. Despite these deviations, we did not see significant increases in the rates of adverse events in patients treated in the extended time window. CONCLUSIONS: Our data are consistent with previously reported international data that IV thrombolysis can safely be used up to 4.5 hours from symptom onset. Restricting the time window to 3 hours would have resulted in almost one-fifth fewer patients treated at our center.