Background: The internet continues to offer new forms of support for health decision making. Government, charity, and commercial websites increasingly offer a platform for shared personal health experiences, and these are just some of the opportunities that have arisen in a largely unregulated arena. Understanding how people trust and act on this information has always been an important issue and remains so, particularly as the design practices of health websites continue to evolve and raise further concerns regarding their trustworthiness.Objective: The aim of this study was to identify the key factors influencing US and UK citizens’ trust and intention to act on advice found on health websites and to understand the role of patient experiences.Methods: A total of 1123 users took part in an online survey (625 from the United States and 498 from the United Kingdom). They were asked to recall their previous visit to a health website. The online survey consisted of an updated general Web trust questionnaire to account for personal experiences plus questions assessing key factors associated with trust in health websites (information corroboration and coping perception) and intention to act. We performed principal component analysis (PCA), then explored the relationship between the factor structure and outcomes by testing the fit to the sampled data using structural equation modeling (SEM). We also explored the model fit across US and UK populations.Results: PCA of the general Web trust questionnaire revealed 4 trust factors: (1) personal experiences, (2) credibility and impartiality, (3) privacy, and (4) familiarity. In the final SEM model, trust was found to have a significant direct effect on intention to act (beta=.59; P<.001), and of the trust factors, only credibility and impartiality had a significant direct effect on trust (beta=.79; P<.001). The impact of personal experiences on trust was mediated through information corroboration (beta=.06; P=.04). Variables specific to electronic health (eHealth; information corroboration and coping) were found to substantially improve the model fit, and differences in information corroboration were found between US and UK samples. The final model accounting for all factors achieved a good fit (goodness-of-fit index [0.95], adjusted goodness-of-fit index [0.93], root mean square error of approximation [0.50], and comparative fit index [0.98]) and explained 65% of the variance in trust and 41% of the variance in intention to act.Conclusions: Credibility and impartiality continue to be key predictors of trust in eHealth websites. Websites with patient experiences can positively influence trust but only if users first corroborate the information through other sources. The need for corroboration was weaker in the United Kingdom, where website familiarity reduced the need to check information elsewhere. These findings are discussed in relation to existing trust models, patient experiences, and health literacy.