For a study, researchers aimed to increase patient safety and quality while reducing burnout through optimizing clinical decision support (CDS) alerts, the Clickbusters effort at Vanderbilt University Medical Center (VUMC). They devised a 10-step Clickbusting procedure and deployed a program that comprised a curriculum, CDS alert inventory, oversight procedure, and game-based learning. At VUMC, they conducted two 3-month cycles of the Clickbusters program. Investigators conducted descriptive evaluations of the modifications made to alerts throughout the procedure and the alert firing rates before and after the program. Before the implementation of Clickbusters, VUMC had 419 CDS alerts in production, with 488,425 firings (42,982 interruptive) every week. After 2 rounds, the Clickbusters program resulted in full, comprehensive assessments of 84 CDS alerts and a decrease of more than 70,000 weekly alert firings (15.43%). In addition to improving CDS directly, the project improved user interest and participation in CDS. At VUMC, the Clickbusters program optimized CDS alerts by decreasing alert firings and subsequent clicks. Additionally, the initiative increased user participation in reviewing and enhancing CDS. It contributed to establishing a culture of continual examination and improvement of clinical information in the electronic health record.