In-hospital onset strokes represent 4% to 20% of all reported strokes in the United States. The variability of treatment protocols and workflows as well as the complex etiology and multiple comorbidities of the in-hospital stroke subpopulation often result in unfavorable outcomes and higher mortality rates compared to those who experience strokes outside of the hospital setting. The purpose of this project was to conduct a systematic review to identify and summarize effective strategies and practices for prompt recognition and treatment of in-hospital strokes. The results of the literature review with leading-edge guidelines for stroke care were corelated to formulate recommendations at an organizational level for improving care delivery and workflow. Peer-reviewed publications and literature not controlled by publishers were analyzed. An appraisal of 24 articles was conducted, using the guide for classification of level of evidence by Fineout-Overholt, Melnyk, Stillwell, and Williamson. The results of this systematic review revealed that the most effective strategies and practices for prompt recognition and treatment of in-hospital strokes included: staff education, creating a dedicated responder team, analysis and improvement of internal processes to shorten the time from discovery to diagnosis, and offering appropriate evidence-based treatments according to acute stroke guidelines. Creating organizational protocols and quality metrics to promote timely and evidence-based care for in-hospital strokes may result in a positive social change by eliminating the existing care disparities between community and in-hospital strokes and improving the health outcomes of this subpopulation of strokes.