BACKGROUND: Web-based content is rapidly becoming the primary source of health care information. There is a pressing need for web-based health care content to not only be accurate but also be engaging. Improved engagement of people with web-based health care content has the potential to inform as well as influence behavioral change to enable people to make better health care choices. The factors associated with better engagement with web-based health care content have previously not been considered. OBJECTIVE: The aims of this study are to identify the factors that affect engagement with web-based health care content and develop a framework to be considered when creating such content. METHODS: A comprehensive search of the PubMed and MEDLINE database was performed from January 1, 1946, to January 5, 2020. The reference lists of all included studies were also searched. The Medical Subject Headings database was used to derive the following keywords: "patient information," "online," "internet," "web," and "content." All studies in English pertaining to the factors affecting engagement in web-based health care patient information were included. No restrictions were set on the study type. Analysis of the themes arising from the results was performed using inductive content analysis. RESULTS: The search yielded 814 articles, of which 56 (6.9%) met our inclusion criteria. The studies ranged from observational and noncontrolled studies to quasi-experimental studies. Overall, there was significant heterogeneity in the types of interventions and outcome assessments, which made quantitative assessment difficult. Consensus among all authors of this study resulted in six categories that formed the basis of a framework to assess the factors affecting engagement in web-based health care content: easy to understand, support, adaptability, accessibility, visuals and content, and credibility and completeness. CONCLUSIONS: There is a paucity of high-quality data relating to the factors that improve the quality of engagement with web-based health care content. Our framework summarizes the reported studies, which may be useful to health care content creators. An evaluation of the utility of web-based content to engage users is of significant importance and may be accessible through tools such as the Net Promoter score. Web 3.0 technology and development of the field of psychographics for health care offer further potential for development. Future work may also involve improvement of the framework through a co-design process.