OBJECTIVE The present study was done to evaluate in vivo effects of an amorphous calcium phosphate (ACP) containing adhesive in reducing enamel demineralization during the early stage of fixed orthodontic treatment. METHODS A triple blinded randomized clinical trial (RCT) was conducted to evaluate enamel demineralization on 255 anterior teeth in 23 patients over a period of 6 months. A split-mouth design was used; half of the anterior teeth were bonded with the ACP containing adhesive and the contralateral teeth received regular adhesive as a control. The enamel demineralization measurements were done at three different time intervals: immediately after bonding (T0), 1 month after bonding (T1), and 6 months after bonding (T2) using the DIAGNOdent device. RESULTS Significant enamel demineralization variations were determined among groups (p < 0.001). The ACP containing adhesive showed significantly lower enamel demineralization than control adhesive. CONCLUSIONS The result of this study suggests a positive effect on the reduction of enamel demineralization when using ACP containing adhesives during orthodontic treatment over regular adhesive.