Alteplase is a tissue plasminogen activator approved for treating acute ischemic stroke (AIS), acute myocardial infarction (AMI), and acute massive pulmonary embolism. Two additional tissue plasminogen activators, tenecteplase and reteplase, are also approved for AMI treatment. However, neither tenecteplase nor reteplase is approved for AIS treatment. The U.S. Food and Drug Administration has received reports of accidental administration of tenecteplase or reteplase instead of alteplase in patients with AIS, which can lead to potential overdose. Primary factors contributing to medication errors include use of the abbreviations "TPA," "tPA," or "TNK" in written or verbal orders and use of these agents in similar settings. Steps to reduce the likelihood of accidental substitution include use of full brand or generic names and inclusion of the indication in written and verbal orders, addition of alerts in automated dispensing machines and ordering systems, and use of stroke boxes containing alteplase and materials for administration.