OBJECTIVE The aim of this prospective study was to test the efficacy of casein phosphopeptide amorphous calcium phosphate (CPP-ACP) paste applied in-office to prevent white spot lesions (WSL) in patients undergoing fixed orthodontic treatment. METHODS Study design: this study was designed as a randomised controlled clinical trial. Fifty-seven patients undergoing nonextraction fixed orthodontic treatment were enrolled and divided randomly into two groups (control n = 28, experimental n = 29). The pretreatment plaque, gingival and bleeding indices, and oral hygiene habits were recorded. One group received CPP-ACP paste (GC Tooth Mousse) at each monthly orthodontic follow-up examination; the control group received routine orthodontic treatment. The mean patient age was 16.9 years in the experimental group and 17.1 years in the control group. The periodontal indices, decayed, missing, and filled teeth (DMFT), decayed, missing, and filled surfaces (DMFS), and the WSL prevalence pre- and post-treatment were measured and compared between the groups. METHODS differences between groups in normally distributed data between groups were assessed by the paired-t test, and the Wilcoxon Signed Rank test was used to compare variables that were not normally distributed. RESULTS There was a lower incidence of WSL in the experimental group compared to the control group. Most of the WSL occurred at the maxillary incisors, mandibular canines and premolars. CONCLUSIONS The in-office application of CPP-ACP paste did not prevent WSL development completely; however, it did significantly decrease the number of WSL compared to the control patients.