Background and Purpose: The approved treatment by the Food and Drug Administration for acute ischemic stroke is intravenous tissue-type plasminogen activator (IV tPA). After IV tPA administration, patients are monitored for adverse events using an American Heart Association/American Stroke Association guideline instituted in 1996. There is limited evidence describing the safest and most efficient method to monitor patients during the first 24 hours after tPA administration. Although the overall rates of adverse events have been reported, the time when patients may be at most risk for an event has not been studied. The purpose of this study was to identify the time of adverse event occurrences in the first 24 hours after IV tPA administration. Method: This was a descriptive, retrospective chart review study of patients admitted to an integrated health system and treated with IV tPA for acute stroke between July 2010 and July 2012. Charts were reviewed for adverse events using the Institute for Healthcare Improvement’s Global Trigger Tool for Measuring Adverse Events. Possible chart indicators of adverse events or “triggers” included neurological decline, vital signs elevated above specified parameters, and emergent imaging. Adverse events included episodes of neurological decline, angioedema, allergic reactions, bleeding, and intracerebral hemorrhage (ICH). The timing of each detected event was determined, and descriptive statistics were used for data analysis. Results: Fourteen adverse events (2.8%) were detected in a population of 498 patients. Reactions consisted of allergic reaction (n = 1), angioedema (n = 1), neurological decline without ICH (n = 1), gastrointestinal bleeding (n = 1), bleeding gums (n = 1), and high-risk ICH (n = 9). Thirteen of the 14 adverse events (92.9%) occurred within the first 12 hours after IV tPA administration. Conclusion: Close monitoring during the first 12 hours after IV tPA treatment may be essential. However, close monitoring after 12 hours may not contribute significantly to improved patient outcomes. Larger studies may provide evidence for the safest and most efficient monitoring protocol for patients treated with IV tPA for ischemic stroke.