The purpose of this study was to identify risk factors to predict caries progression in toddlers in primary-healthcare settings for the cost-effective targeting of preventive and referral strategies. We examined 329 children (26 ± 6 mos old) twice, one year apart, in Indiana, USA. A 107-item structured interview was used to collect information from the primary caregiver and child on factors/beliefs/perceptions/behaviors that could affect caries development, transmission of bacteria, medical-dental health, and access to care. Bacterial levels, gingivitis, dental plaque, and caries experience were assessed. Multiple-variable logistic regression models of caries progression toward cavitation included family caries experience, transmission-related behaviors, dietary factors, health beliefs, and lower income, but differed in selected predictors/predictive power by race/ethnicity. Addition of clinical variables did not significantly improve the prediction.