Objective: To evaluate the in vivo potential of xylitol to reduce plaque acidogenicity in comparison to sorbitol. Method and Materials: After completing a questionnaire on general health, smoking, diet, and oral hygiene habits, 61 dentate adults refrained from oral hygiene for 3 days before the clinical baseline examination, which included decayed, missing, and filled teeth (DMFT) index, mutans streptococci and lactobacilli counts, and plaque acidogenicity (cH) index after a sucrose rinse. Then the participants were randomly allocated to consume either sorbitol or xylitol lozenges (5 pieces/day, 2 g each) for 4 weeks and were asked to refrain from oral hygiene for the 3 days prior to the final examination (cH, area pH 7, bacterial counts). Results: The variation of acidogenicity in different individuals was considerable at baseline (range: 0.2 to 446.6 min*µmol/L) with a mean value of 37.9 ± 58.9 min*µmol/L for the sorbitol group and 60.6 ± 87.6 min*µmol/L for the xylitol group. At the end of the study, the reduction in the xylitol group (42.9 ± 80.6 min*µmol/L) was statistically significantly higher than in the sorbitol group (6.0 ± 69.4 min*µmol/L, P = .034), which was also confirmed in an additional analysis excluding 2 participants with extreme values (reduction for xylitol: 29.5 ± 36.9 min*µmol/L; sorbitol: 1.7 ± 57.0 min*µmol/L; P = .019). Statistically significant differences were also found for the area below pH 7 (reduction for xylitol: 10.8 min pH; sorbitol, 0.2 min pH; P = .0025). Conclusion: The regular consumption of xylitol lozenges modifies dental plaque, resulting in a marked reduction in the plaque acidogenicity, which could not be detected using sorbitol lozenges. Therefore, xylitol could have an additional benefit in caries prevention. Keywords: acidogenicity, caries, cH index, plaque, prevention, sorbitol, xylitol