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Background Intravenous (IV) tissue plasminogen activator (tPA) utilization in acute ischemic stroke (AIS) requires weight-based dosing and a standardized infusion rate. In our regional network, we have tried to minimize tPA dosing errors. We describe the frequency and types of tPA administration errors made in our comprehensive stroke center (CSC) and at community hospitals (CHs) prior to transfer. Methods Using our stroke quality database, we extracted clinical and pharmacy information on all patients who received IV tPA from 2010-11 at the CSC or CH prior to transfer. All records were analyzed for the presence of inclusion/exclusion criteria deviations or tPA errors in prescription, reconstitution, dispensing, or administration, and for association with outcomes. Results We identified 131 AIS cases treated with IV tPA: 51% female; mean age 68; 32% treated at the CSC, and 68% at CHs (including 26% by telestroke) from 22 CHs. tPA prescription and administration errors were present in 64% of all patients (41% CSC, 75% CH, P P Conclusion Despite focus on minimization of tPA administration errors in AIS patients, such errors were very common in our regional stroke system. Although an association between tPA errors and stroke outcomes was not demonstrated, quality assurance mechanisms are still necessary to reduce potentially dangerous, avoidable errors.