The purpose of this study was to evaluate the cost-effectiveness of two preventive interventions aimed at increasing the proportion of caries-free preschool children of low socioeconomic status using a decision analytic model. Two scenarios were tested, one with a school milk program (SMP) and one without (non-SMP). Fluoride varnish (FV) and a probiotic (PB) were compared to a do-nothing alternative among children in public nurseries/schools over a 4-year period. FV was applied biannually and a PB (Lactobacillus rhamnosus) added to milk powder prepared daily. A Markov decision tree model was utilized. Several sources of data were used to populate the model. Probabilistic and deterministic sensitivity analyses were performed, and a public provider perspective was used. In the SMP scenario, PB was more effective and less costly than FV and, compared with do-nothing, increased the proportion of caries-free children by 14.5%, with a cost of USD 12.5 per child (June 2018). PB presented an incremental cost-effectiveness ratio (ICER) or cost per extra caries-free child of USD 86.2. In the non-SMP scenario, both interventions were cost-effective. FV (compared with do-nothing) increased the percentage of caries-free children by 8.3% with an ICER of USD 338.3 and PB (compared with FV) increased the effect by 6.2% with an ICER of USD 1400.2. The findings showed that PB was most effective and less costly than FV in the SMP scenario only. This type of analysis and its results provide essential information for decision-makers to improve the oral health of preschool children.