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 Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn.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: The eHealth Literacy Scale (eHEALS) is a tool for the self-assessment of perceived comfort and skills in using the Internet as a source for health-related information. Although evidence exists of reliability, construct and structural validity of the scale, there is a lack of evidence for criterion validity in relation to what is proposed by Norman and Skinner in their theoretical model of eHealth literacy (lily model), in particular it is not clear whether having more health literacy can positively influence eHealth literacy as measured by the eHEALS. Objective: Our study aim was to assess whether real-life experiences in the area of health, as a proxy of higher health literacy, could influence eHealth literacy as measured using the eHEALS and proposed in the lily model of e-health literacy, while also validating the scale in the adult Italian population by exploring its internal consistency and component structure. Methods: Two web-based surveys were conducted among adults living in Northeast Italy. In order to be able to measure the impact of a real-life experience in the health field, we divided our sample into two groups, respectively characterized by experience in studying or working in the health sector and by lack thereof. Results: We recruited a total of 1135 subjects, of which 326 were included in the group with studying and working experiences in the health field. After removing subjects who didn’t complete the whole eHEALS, a total of 868 eHEALS respondents were included for further analysis. Mean eHEALS total score was 28.2±6.2 for the whole sample, with statistically significant differences (P<.001) between the two groups, with the higher health literate group scoring significantly better (31.9±5.9 vs 26.7±5.6). Cronbach alpha was high for all groups (.90 for the whole sample of eHEALS respondents, and .91 and .87 for the two groups separately), and Principal Factor Component analysis showed good factor loadings for all items ranging from 0.68 to 0.83 in the whole sample, with an eigenvalue of 4.90 explaining 61% of the total variability. Analysis of convergent validity showed results in line with current literature, with a significant, yet moderate, correlation of eHEALS score with frequency of Internet use for health-related purposes. Conclusions: The study demonstrated health literacy positive influence on eHEALS results and its complex relation with eHealth literacy, corroborating what was initially proposed by Norman and Skinner in the lily model. Also, we have been able to test an alternative Italian translation of the eHEALS (IT-eHEALS), which can be used as a valid tool to measure eHealth literacy in the adult Italian population.