BACKGROUND Patients with symptoms that impersonate a stroke but are later found to have an alternate diagnosis are termed stroke mimics. Stroke mimics treated with intravenous (IV) tissue plasminogen activator (t-PA) are exposed to hemorrhagic complications without benefit. The objective of this study is to describe the characteristics, safety, and outcomes of stroke mimic patients treated with t-PA within 4.5 hours. METHODS All patients hospitalized after IV t-PA treatment at a tertiary care hospital and primary stroke center from January 2008 through December 2011 were reviewed. Stroke mimics were determined by review of clinical and imaging findings. Stroke mimics are described and compared with acute ischemic stroke patients for demographics, clinical characteristics, and bleeding complications. RESULTS We identified 38 stroke mimic (12%) and 285 ischemic stroke (88%) t-PA-treated patients. Compared with ischemic stroke patients, mimic patients were younger, more often female, and reported a history of stroke more often. There were no differences in race, baseline stroke scale, or onset to treatment time. There were no intracerebral hemorrhages or deaths in the mimic patients but there were 2 systemic hemorrhages (5.2%). CONCLUSIONS Treatment of mimic patients with IV t-PA appears to be safe in this cohort. Concern for intracerebral hemorrhage in mimic patients need not dissuade clinicians from administering t-PA when significant concern for ischemic etiology exists.