Health care systems have encountered unprecedented challenges during the coronavirus disease-2019 (COVID-19) pandemic, such as standardizing care in the absence of high-quality data. As an emblematic example, preliminary data and early anecdotal experience suggested that a major driver of COVID-19 pathophysiology was hypercoagulability, suggesting the need for aggressive anticoagulation. In this article, we describe the rapid guidance process for the development of an anticoagulation protocol for COVID-19. Preliminary evidence was collected from multidisciplinary experts within our institution to inform the first protocol draft. After implementation, we rapidly acquired data to inform a revision, with subsequent modifications based on higher quality data. The description of this process can inform other health systems when faced with a similar crisis characterized by high patient volumes, poor clinical outcomes, lack of proven effective therapies, and rapid flow of information from multiple sources of variable credibility.