BackgroundAs SARS-CoV-2, the virus that causes COVID-19, spread rapidly across the United States in the spring of 2020, institutions of higher education faced numerous challenges associated with minimizing risk of exposure to COVID-19 among their students, faculty, staff, and surrounding communities. This paper describes the protocol, South Carolina (SC) Safer Together, developed by Clemson University (Clemson) to design, deploy, and evaluate multi-level communication and dissemination and implementation (D&I) strategies in line with recommendations from governmental and educational agencies to mitigate the risk of exposure to COVID-19. Safer Together was enhanced by the addition of the Google/Apple Exposure Notification app, an alternative strategy to support a recommendation of COVID-19 testing outcomes: contact tracing, isolation, and quarantine.ObjectiveThis study aimed to (1) describe the content and intended audiences of D&I strategies used to deploy recommended COVID-19 mitigation strategies on a major college campus; (2) determine the reach, acceptability, adoption, and use of D&I strategies among target audiences among university students, faculty, and staff; and (3) characterize barriers and facilitators to the implementation and use of recommended mitigation strategies.MethodsThe study team incorporated elements of the Health Belief Model, the Technology Acceptance Model, communication and social marketing models, and the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to identify and develop appropriate constructs and specific outcomes for inclusion in our approach to evaluate the communication, dissemination and implementation processes related to deployment of Safer Together at Clemson. A parallel convergent mixed methods design was used to (1) inform implementation strategies used to launch the program and (2) evaluate program reach, acceptability, adoption, and use guided by the RE-AIM framework. Data collection tools include surveys, data analytics–tracking, and focus groups or interviews with key stakeholders (students, employees, and university leadership).ResultsRigorously studying both the dissemination and implementation of Safer Together in a national public university setting is expected to yield lessons that will be valuable at many organizational and governmental settings. On a local level, broad adoption and use of the Safer Together may help reduce COVID-19 transmission and keep the university “open.” On a larger scale, lessons learned on how to influence student and employee behavior with respect to the use of a public health outbreak prevention tool including Safer Together may be applicable in future pandemic and outbreak situations.ConclusionsThis study proposes a structured, theory-driven approach to evaluate dissemination and implementation strategies associated with the deployment of Safer Together in a university setting from the viewpoint of students, employees, and university leadership. Our results will inform future implementation of apps such as Safer Together at major state universities in SC.International Registered Report Identifier (IRRID)DERR1-10.2196/32567