Background: Web-based interventions provide the opportunity to combine the tailored approach of face-to-face interventions with the scalability and cost-effectiveness of public health interventions. This potential is often limited by low engagement. A number of studies have described the characteristics of individuals who engage more in Web-based interventions but few have explored the reasons for these variations. Objective: We aimed to explore individual-level factors associated with different degrees of engagement with a Web-based behavior change intervention following provision of coronary heart disease (CHD) risk information, and the barriers and facilitators to engagement. Methods: This study involved the secondary analysis of data from the Information and Risk Modification Trial, a randomized controlled trial of a Web-based lifestyle intervention alone, or alongside information on estimated CHD risk. The intervention consisted of three interactive sessions, each lasting up to 60 minutes, delivered at monthly intervals. Participants were characterized as high engagers if they completed all three sessions. Thematic analysis of qualitative data from interviews with 37 participants was combined with quantitative data on usage of the Web-based intervention using a mixed-methods matrix, and data on the views of the intervention itself were analyzed across all participants. Results: Thirteen participants were characterized as low engagers and 24 as high engagers. There was no difference in age (P=.75), gender (P=.95), or level of risk (P=.65) between the groups. Low engagement was more often associated with: (1) reporting a negative emotional reaction in response to the risk score (P=.029), (2) perceiving that the intervention did not provide any new lifestyle information (P=.011), and (3) being less likely to have reported feeling an obligation to complete the intervention as part of the study (P=.019). The mixed-methods matrix suggested that there was also an association between low engagement and less success with previous behavior change attempts, but the statistical evidence for this association was weak (P=.16). No associations were seen between engagement and barriers or facilitators to health behavior change, or comments about the design of the intervention itself. The most commonly cited barriers related to issues with access to the intervention itself: either difficulties remembering the link to the site or passwords, a perceived lack of flexibility within the website, or lack of time. Facilitators included the nonjudgmental presentation of lifestyle information, the use of simple language, and the personalized nature of the intervention. Conclusions: This study shows that the level of engagement with a Web-based intervention following provision of CHD risk information is not influenced by the level of risk but by the individual’s response to the risk information, their past experiences of behavior change, the extent to which they consider the lifestyle information helpful, and whether they felt obliged to complete the intervention as part of a research study. A number of facilitators and barriers to Web-based interventions were also identified, which should inform future interventions.