To determine the efficacy of topical applications of 10% casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste in reverting white spot lesions (WSLs) after fixed orthodontic treatment. Forty one participants were randomly assigned to either the test group (CPP-ACP) or the control group (only fluoride toothpaste). All patients used regular fluoride-containing toothpaste. CPP-ACP paste or fluoridated toothpaste was applied on to tooth surfaces with WSLs twice a day during 36-month after de-bonding. The labial/buccal surfaces of teeth were assessed by use of DIAGNOdent pen (DD), Gorelick Index and ICDAS II criteria at baseline (T1) and 36-month (T2) follow-up visits. The total counts of Streptococcus mutans and Lactobacillus were obtained at T1 and T2. DMFT, DMFS, stimulated flow rate and buffer capacity were calculated in two appointments. Daily usage of CPP-ACP paste was not better than normal care for improving the appearance of WSLs after 36 months.