High fluoride dentifrice (FD; 5,000 ppm F) has been recommended to arrest root dentine lesions and to control enamel caries in high-risk patients. Also, standard FD (1,100 ppm F) in combination with professional fluoride application has been recommended to control dentine caries, but the effect of this combination on enamel has been considered modest. Considering the lack of evaluation comparing the use of 5,000 ppm FD (5,000-FD) versus acidulated phosphate fluoride (APF) application combined with 1,100 ppm FD (1,100-FD) on the inhibition and repair of caries lesions in both enamel and dentine, we conducted this in situ, double-blind, crossover study of 3 phases of 14 days. In each phase, 18 volunteers wore palatal appliances containing enamel and root dentine specimens, either sound or carious, to evaluate the effect of the treatments on the inhibition or repair of caries lesions, respectively. The treatments were non-FD (negative control), 5,000-FD, or 1 APF gel application on dental specimens combined with 1,100-FD used twice per day (APF + 1,100-FD). The reduction of demineralization and enhancement of remineralization were assessed by surface and cross-sectional hardness. Fluoride concentration was determined on dental specimens and on the formed biofilm. For enamel, APF + 1,100-FD and 5,000-FD did not differ regarding the inhibition of demineralization and repair of caries lesions. However, for dentine the difference between these treatments was inconclusive because while APF + 1,100-FD was more effective than 5,000-FD in caries lesion reduction and repair, 5,000-FD was more effective than APF + 1,100-FD in the reduction of surface demineralization. Therefore, the findings show that the combination of APF + 1,100-FD is as effective as 5,000-FD in enamel inhibition of demineralization and enhancement of remineralization.