The purpose of this Institutional Review Board-approved study was to identify risk factors of caries lesion progression in children enrolled in rural schools in Puerto Rico. A convenience sample of 408 children (5-13 yrs old) was examined at baseline and at 12 and 24 mos with the International Caries Detection and Assessment System (ICDAS). A total of 395 caregivers completed a 25-item questionnaire including socio-demographic, dietary, protective factors, disease experience, and access to care. Caries progression was significant (89% and 91% at 12 and 24 mos, respectively). Multiple-variable models for predicting children with lesion progression and numbers of lesions progressing were calculated for 2 outcome variables (any-progression vs. progression-toward-cavitation). Models developed had areas under the receiver operating characteristic (ROC) curve ranging between 0.70 and 0.79 and were very similar regardless of the outcome (progression criteria), prediction time (12-24 mos), or inclusion (or not) of previous caries experience. Significant predictors of disease progression collected through a parent-completed questionnaire included questions related to caries experience in the child or caregiver, and the caregiver's rating of the child's oral health.