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Background— National guidelines endorse recombinant tissue-type plasminogen activator (r-tPA) in eligible patients with acute ischemic stroke to improve patients’ functional recovery. However, 23% to 40% of ideal candidates with acute ischemic stroke for reperfusion are not treated, perhaps because of the difficulty in explaining the benefits and risks of r-tPA within the frenetic pace of emergency department care. To support better knowledge transfer and creation of a shared decision-making tool, we conducted qualitative interviews to define the information needs and preferred presentation format for stroke survivors, caregivers, and clinicians considering r-tPA treatment. Methods and Results— A multidisciplinary team used qualitative research methods to identify informational needs and strategies for describing the benefits and risks of r-tPA in a clinical setting. Through focus groups (n=10) of stroke survivors (n=39) and caregivers (n=24) and individual interviews with emergency physicians (n=23) and advanced practice nurses (n=20), several themes emerged. Survivors and caregivers preferred a broader definition of a good outcome (independence, rather than no significant disability), simpler graphs as compared with detailed pictographs, and presentation of both population and individualized benefits (framed positively) and risk of receiving r-tPA. Some physicians expressed skepticism with the data and the ability to present risk/benefit information emergently, whereas other physicians and most advanced practice nurses thought such information would improve care. Physicians stressed the importance of presenting the risk of thrombolytic-related intracranial hemorrhage. Conclusions— This study suggests that a positively framed risk–benefit tool with graphical presentations of general and patient-specific risk estimates could support patients and providers in considering r-tPA for acute ischemic stroke. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01864928.