ABSTRACT: Internet interventions have the potential to address many of the health problems that produce the greatest global burden of disease. We present a study illustrating this potential. The Spanish/English San Francisco Stop Smoking Internet site, which yielded quit rates of 20% or more at 12 months in published randomized controlled trials (RCTs), was modified to make it accessible to Spanish- and English-speaking smokers 18 years of age or older anywhere in the world.To illustrate that Internet interventions designed to conduct RCTs can be adapted to serve as universal health care resources. We also examine quit rates obtained in the current participant preference study (in which users could choose from all elements tested in previous RCTs) to determine whether they differ from the quit rates found in the RCTs.We modified the San Francisco Stop Smoking Internet site so that, instead of being randomly assigned to a specific intervention, participants could personalize the site by choosing among nine site elements (eg, stop smoking guide, reminder emails, journal, mood management intervention, or virtual group). Participants completed a baseline assessment, and reported smoking and mood data at 1-, 3-, 6-, and 12-month follow-ups. We assessed the modified website's reach and outcomes (quit rates), and compared the quit rates of the current participant preference study with those of the previous RCTs.In the first year of recruitment, 94,158 individuals from 152 countries and territories visited the site; 13,488 participants left some data; 9173 signed consent; 7763 completed the baseline survey; and 1955, 1362, 1106, and 1096 left 1-, 3-, 6-, and 12-month data, respectively. Observed quit rates were 38.1% (n = 668), 44.9% (n = 546), 43.6% (n = 431), and 45.4% (n = 449), respectively. The current participant preference study yielded higher observed quit rates (odds ratio 1.30) than the previous RCT when controlling for individuals' demographic and smoking characteristics.After strict RCTs are completed, Internet intervention sites can be made into worldwide health intervention resources without reducing their effectiveness.Clinicaltrials.gov NCT00721786; http://clinicaltrials.gov/ct2/show/NCT00721786 (Archived by WebCite at http://www.webcitation.org/66npiZF4y).