ObjectiveThe aim of this study was to evaluate the effect of fluoride dentifrices combined with sodium hexametaphosphate (HMP) on enamel demineralization in vitro.Material and methodsEnamel bovine blocks were selected by initial surface hardness (SHi) and then divided into five experimental groups (n = 12): placebo (without fluoride and without HMP); 1100 ppm F (1100F); and 1100F associated with HMP at 0.5 % (1100HMP0.5%), 1 % (1100HMP1%), and 2 % of HMP (1100HMP2%). Blocks were submitted to five pH cycles (demineralizing/remineralizing solutions) at 37 °C. After pH cycling, final surface hardness (SHf), percentage of surface hardness loss (%SH), integrated differential hardness (ΔIH), integrated loss of subsurface hardness (ΔKHN), and enamel firmly bound fluoride (F) were determined. Data were submitted to one-way ANOVA, followed by Student–Newman–Keuls test (p < 0.05).ResultsSignificant differences were observed among all groups regarding %SH and ΔKHN. 1100HMP1% promoted the lowest mineral loss among all groups (p < 0.001), and led to significantly lower demineralization in the deeper regions of the subsurface lesion when compared with the other HMP-containing toothpastes (p < 0.001). Significantly higher mineral loss was observed for 1100HMP2% when compared to the other fluoridated dentifrices, mainly in the outer part of the lesion (p < 0.001). Enamel F uptake was similar for 1100F and 1100HMP1% but significantly reduced for other HMP concentrations.ConclusionThe supplementation of a 1100-ppm F dentifrice with 1 % HMP promoted a higher inhibitory effect against enamel demineralization when compared to a dentifrice containing the same amount of fluoride in vitro.Clinical relevanceThis dentifrice could potentially be indicated to patients at high risk of caries.