Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: With increased access to technology and the Internet there are many opportunities for utilizing e-health, Internet or technology-delivered health services and information, for the prevention and management of chronic diseases. Objective: The purpose of this paper is to explore (1) the differences in technology use, (2) online health information seeking and use behaviors, (3) attitudes towards seeking health information online, and (4) level of e-health literacy between adults aged 18-64 with and without chronic disease(s). Methods: A cross-sectional, Internet survey was conducted in March 2017 with 401 U.S adults. Participant responses were examined to understand associations between chronic disease status and e-health behaviors such as Internet health-seeking behaviors and online behaviors related to health, tracking health indicators with a mobile app, patient portal use, and preferences for health information. Results: About one in three (37.2%) participants reported at least one chronic disease diagnosis. Around 75% of all participants reported having ever searched for health information online. Participants with a chronic disease reported significantly higher instances of visiting and talking to a healthcare provider based on health information found online (40.0% vs. 25.8%, X2(2)=6.65, p=.01; 43.3% vs. 27.9%, X2(2)=7.58, p=.006). The uses of health information found online also significantly differed between participants with and without chronic diseases in affecting a decision about how to treat an illness or condition (49.2% vs. 35.0%, X2(3)=6.66, p=.04), changing the way they cope with a chronic condition or manage pain (40.8% vs. 19.4%, X2(2)=16.33, P<.001), and leading them to ask a doctor new questions or get a second opinion (37.5% vs. 19.6%, X2(2)=11.8, p<.001). Chronic disease participants were significantly more likely to be tracking health indicators (43.9% vs. 28.3%, X2(2) = 10.42, p=.006). Around 24% of all participants reported using a health related mobile app. In addition, participants with a chronic disease diagnosis reported significantly higher rates of patient portal access (55.0% vs 42.1%, X2(2)=6.33, p=.01) and use (40.9% vs 21%, X2(2)=18.24, P<.001). Lastly, both groups reported similar perceived skills in using the Internet for health information on the eHEALS health literacy scale. Higher eHEALS average scores also were significantly associated with e-health behavior engagement in both groups. The majority of participants responded positively when asked about the usefulness of health information and importance of accessing health resources online. Conclusions: The high rates of reported information seeking and use of Internet-based health technology among participants with chronic disease may reflect the uptake in e-health to help manage chronic disease conditions. Healthcare providers and educators should continue to seek ways to interact and support patients in their management of chronic disease through e-health platforms, including capitalizing on online resources, patient portals, and smartphone apps for disease education and monitoring.