Background. Although caries is prevalent in adults, investigators have tested few preventive therapies in adult populations. In a randomized controlled trial, the authors evaluated the effectiveness of xylitol lozenges in preventing caries in adults at elevated risk of developing caries. Methods. The Xylitol for Adult Caries Trial (X-ACT) was a three-site placebo-controlled randomized trial. Participants (n = 691) aged 21 through 80 years consumed five 1.0-gram xylitol or placebo lozenges daily for 33 months. They underwent clinical examinations at baseline and at 12,24 and 33 months. Results. Xylitol lozenges reduced the caries increment 10 percent. This reduction, which represented less than one-third of a surface per year, was not statistically significant. There was no indication of a dose-response effect. Conclusions. Daily use of xylitol lozenges did not result in a statistically or clinically significant reduction in 33-month caries increment among adults at an elevated risk of developing caries. Clinical Implications. These results suggest that xylitol used as a supplement in adults does not reduce their caries experience significantly.