Objective: The aim of this study was to test the efficacy of long-term, daily intake of erythritol and xylitol candy, compared with sorbitol candy, on the development of enamel and dentin caries lesions. Methods: The study was a double-blind randomized controlled prospective clinical trial. Altogether 485 primary school children, first- and second-graders at baseline, from southeastern Estonia participated in this 3-year intervention. Each child consumed four erythritol, xylitol or sorbitol (control) candies three times per school day. The daily intake of polyol was about 7.5 g. The International Caries Detection and Assessment System (ICDAS) was used in the clinical examinations by four calibrated examiners at baseline and at 12, 24 and 36 months. Results: The annual examination analyses and the follow-up analyses confirmed that the number of dentin caries teeth and surfaces at 24 months follow-up and surfaces at 36 months follow-up was significantly lower in the mixed dentition in the erythritol group than in the xylitol or control group. Time of enamel/dentin caries lesions to develop and of dentin caries lesions to progress was significantly longer in the erythritol group compared to the sorbitol and xylitol groups. Also the increase in caries score was lower in the erythritol group than in the other groups. Conclusions: In the follow-up examinations, a lower number of dentin caries teeth and surfaces was found in the erythritol group than in the xylitol or control groups. Time to the development of caries lesions was longest in the erythritol group. Trial registration: ClinicalTrials.gov Identifier NCT01062633.