"This paper describes an infodemic management system workflow based on digital data collection, qualitative methodology, and human-centered systems to support the COVID-19 vaccine rollout in Ghana with examples of system implementation. Methods: The infodemic management system was developed by the Health Promotion Division of the GHS and the UNICEF Country Office. It uses Talkwalker, a social listening software platform, to collect misinformation on the web. The methodology relies on qualitative data analysis and interpretation as well as knowledge cocreation to verify the findings. A multi-sectoral National Misinformation Task Force was established to implement and oversee the misinformation management system. Two members of the task force were responsible for carrying out the analysis. They used Talkwalker to find posts that include the keywords related to COVID-19 vaccine–related discussions. They then assessed the significance of the posts on the basis of the engagement rate and potential reach of the posts, negative sentiments, and contextual factors. The process continues by identifying misinformation within the posts, rating the risk of identified misinformation posts, and developing proposed responses to address them. The results of the analysis are shared weekly with the Misinformation Task Force for their review and verification to ensure that the risk assessment and responses are feasible, practical, and acceptable in the context of Ghana." (Abstract)