BackgroundClinical trials are critical to scientific advances and medical progress, although awareness and participation remain low in the general population. The existing literature indicates that clinical trial knowledge and participation is multifactorial. Yet, little is known about the association between clinical trial participation with health technology use and digital health engagement to search for health information, interact with medical providers, and seek health supports.ObjectiveExamine the multivariate association between clinical trial knowledge and participation with past-year health technology use and digital health engagement with medical providers.DesignCross-sectional data from a federal surveillance system.ParticipantsA total of 3,865 US adult respondents from the Health Information National Trends Survey 5, Cycle 4 conducted in 2020.Main MeasuresThe two outcomes were clinical trial knowledge (no knowledge, a little knowledge, a lot of knowledge) and participation (never invited, invited did not participate, invited and participated). There were four binary indicators of health technology use for the following purposes in the past year: searching for health or medical information, communicating with a doctor’s office, looking up medical test results, and making medical appointments. There were four binary indicators of digital health engagement in the past year: sharing health information on social media, participating in a health forum or support group, watching health-related videos on YouTube, and awareness of ClinicalTrials.gov.Key ResultsSurvey-weighted multivariate regression models demonstrated that awareness of ClinicalTrials.gov had the largest associations with clinical trial knowledge and participation. Digital technology use to engage with medical providers and electronic health records was associated with clinical participation, although the vast majority of respondents had never been invited.ConclusionsFindings from this study can inform the design of large-scale digital health campaigns and quality improvement programs focused on increasing clinical trial participation.