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Background: Patients presenting with altered mental status, syncope, and other non-localizing complaints may be subsequently diagnosed with minor ischemic or hemorrhagic strokes. These patients, termed stroke chameleons, are typically admitted to non-neurology units (NNUs) with a non-stroke diagnosis and are more likely to fall-out on stroke core measures (SCM). Early identification of these patients should improve SCM compliance and promote better care.Methods: A performance improvement initiative was implemented to elevate SCM compliance overall by targeting patients admitted to NNUs in a comprehensive stroke center. A nurse practitioner was dedicated to scan the electronic medical record for potential stroke chameleons on NNUs and review radiology reports to confirm a stroke diagnosis. A SCM checklist was utilized to reinforce SCM adherence with the patient’s providers and nurses. SCM compliance for 24 months pre and 12 months post intervention was compared using data entered into the Get With The Guideline-Stroke database.Results: Over the 3-year study period, 3,355 patients were discharged with a stroke diagnosis. Comparing pre to post intervention periods, 522/2129 (24.5%) vs. 401/1226 (32.7%) patients were admitted to NNUs. Distribution of pre- and post intervention stroke diagnoses were ischemic/TIA 381 (73.0%) vs. 319 (79.6%) and hemorrhagic 141 (27.0%) vs. 82 (20.4%). For NNU patients, the initiative had a statistically significant impact on stroke education documentation (45.5% pre vs. 67.0% post; p=0.0006). In addition, compliance improved for smoking cessation (77.8% to 81.2%), early antithrombotics (84.0% to 85.3%), VTE prophylaxis (90.8% to 94.7%), and discharge antithrombotic therapy (98.7% to 100%), although none were statistically significant.Conclusion: Dedicating resources to identify stroke chameleons early, and focusing compliance efforts on NNUs, significantly improved compliance with stroke education. Other SCM showed numerical improvements, but did not reach statistical significance. Especially in centers with high volumes of stroke chameleons, attention and efforts directed at this population raises the quality of care provided to all hospitalized stroke patients.