This double-blind randomized control trial aimed to compare the effects of fluoride varnish with xylitol-coated calcium and phosphate versus fluoride varnish on dental caries increment and transition among preschool children over a period of 6 months. Participants were high caries risk children with at least one erupted tooth, aged not more than 3 years, in Muang District of Khon Kaen. The participants were blocked randomized into two groups (n=120 each) to receive either fluoride varnish with xylitol-coated calcium and phosphate or fluoride varnish every 3 months. Data were collected from guardians using structured questionnaire at baseline. Dental caries were examined using modified ICDAS II. Caries increments were compared at 6 months using Mann-Whitney U test, and caries transition using Generalized Estimating Equations. The results indicated no statistically significant difference in the mean caries increment between the two groups (p>0.05). The transition of enamel caries lesions to the state of regression or stable was not different between groups (p>0.05). The results showed no differences between the two types of fluoride varnish in caries prevention among preschool children at 6-month follow-up. Further evaluation is needed to compare their longer-term effects.