Objective The primary purpose of this study was to assess the cost-effectiveness of caries preventive interventions. Material and methods A systematic review was conducted, following the PRISMA Statement. Four electronic databases were searched (final search 16 March 2020). Studies fulfilling the inclusion criteria were independently critically appraised, by two reviewers in parallel. Data from each included study were extracted and tabulated: the analysis used a narrative approach to present the results of the estimated cost-effectiveness. Results and conclusions Twenty-six publications fulfilled the inclusion criteria and were of low or moderate risk of bias. Ten publications were economic evaluations, directly based on empirical studies, and the other 16 were modelling studies. Most of the studies concerned interventions for children and the most common were analyses of fluoride varnish and risk-based programs. Some of the studies showed both reduced cost and improved outcomes, but most studies reported that the improved outcome came with an additional cost. The results disclosed several cost-effectiveness evaluations of caries preventive interventions in the literature, but these target primarily children at high risk. There is a scarcity of studies specifically targeting adults and especially the elderly.