Background and Purpose— The American Heart Association/American Stroke Association guidelines recommend intravenous tissue-type plasminogen activator (tPA) treatment 3 to 4.5 hours from symptom onset according to criteria used in the Third European Cooperative Acute Stroke Study (ECASS III). However, ECASS III excluded certain patient groups in addition to the standard exclusions used for 0 to 3 hours in the United States: age >80 years, history of stroke and diabetes mellitus, oral anticoagulant treatment, and National Institutes of Health Stroke Scale >25. We investigated adherence to these additional exclusion criteria for patients treated 3 to 4.5 hours from onset and their association with outcome. Methods— We analyzed data from Get With The Guidelines-Stroke on 32 019 patients with ischemic stroke from 1464 hospitals who were treated with tPA ≤4.5 hours from onset from January 2009 to January 2012, excluding patients transferred from another hospital. The percent of patients meeting versus not meeting each exclusion criterion were compared between treatment time windows. Results— Overall, 1544 of 4910 (31.5%) patients treated with tPA >3 to 4.5 hours had at least 1 of the additional exclusions, the most common was age >80 years. With the exception of prior stroke and diabetes mellitus, the percent of tPA–treated patients with each exclusion criterion was significantly lower at >3 to 4.5 hours compared with 0 to 3 hours. For each additional exclusion criterion, there was no increased risk of symptomatic intracranial hemorrhage or worse hospital outcome for patients treated >3 to 4.5 hours compared with 0 to 3 hours, after adjusting for baseline differences. Conclusions— Patients with ECASS III–specific exclusion criteria for the >3 to 4.5 hours window are frequently treated with tPA. The presence of the additional exclusion criteria was not associated with worse outcomes in the >3 to 4.5 hours window compared with the 0 to 3 hours window.