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BACKGROUD Corrosion of metal orthodontic appliances caused by professional fluoride products has been recently concerned. Therefore, the objective of this study was to evaluate the cytotoxic and genotoxic effect of these products on buccal mucosal cells from patients wearing fixed orthodontic appliances. METHODS A total of 44 patients, aged 12 to 35 years, who began orthodontic treatment with fixed appliances were included in this single-center, prospective, randomized clinical trial. Patients were randomly allocated into 4 parallel groups according to the type of professional fluoride treatment applied after placing the appliances: acidulated phosphate fluoride gel (APF); neutral fluoride gel (NGel); fluoride varnish (FVa); and without fluoride treatment (control). Buccal cells were collected before treatment (T1) and 3 months after appliance placement (T2). The cells were assayed for cell viability and underwent Papanicolaou staining. Cells with micronuclei and degenerative nuclear alterations were scored using a light microscope. Cell metal content was quantified by inductively coupled plasma-mass spectrometry. The data were analyzed with the Kruskal-Wallis test. RESULTS The intracellular nickel content in the APF group significantly increased (P < 0.05), whereas that of the control, NGel, and FVa groups did not. The changes in chromium concentration in all groups were not significantly different compared with control. Use of APF resulted in a significantly higher decrease in cell viability and increase in morphologic signs of cell death compared with control (P < 0.05). The change in frequency of micronucleated cells was not significantly different from that in the control group. CONCLUSIONS Applying APF gel on fixed orthodontic appliances increased the cell metal content and decreased cell viability; however, genotoxic effects were absent. FVa and NGel are suggested as the products of choice to use during orthodontic treatment.