In this work, a comprehensive study of risk factors and caries infestation was carried out. The main indicators of the enamel–plaque–saliva system and the state of local immunity in preschoolers with different levels of caries health and activity were studied. The role of regular intake of fluoridated milk in the prevention of caries in children with different levels of health and activity of dental caries has been studied. The study of caries resistance, the main parameters of the cariesogenic situation, and local immunity in preschoolers with different levels of health and activity of dental caries in the dynamics of the systemic use of fluoridated milk. It is stated that in frequently and long-term ill children, the prevalence of general and local risk factors for the development of caries and the intensity of tooth damage is higher, and the caries resistance of enamel is lower than in rarely and occasionally ill children. The use of fluoridated milk in children from the age of 3 is an effective method of primary prevention of dental caries in preschoolers, however, does not completely solve the problem of prevention of caries of baby teeth. The milk fluoridation program is more effective for rarely and occasionally ill children with I degree of caries activity. For frequently and long-term ill children, both with I and III degrees of caries activity, the milk fluoridation program should be supplemented with the use of a set of additional caries-prophylactic measures.