Purpose: To evaluate the effect of a novel antibacterial and fluoride-releasing adhesive formulation on enamel demineralization under sucrose exposure in situ (simulating high caries risk conditions). Materials and Methods: This crossover, blind study was performed in two phases of 14 days. Volunteers (n = 14) wore an intraoral appliance containing four bovine enamel blocks with cavity preparations restored using self-etching primers/composite resin (Clearfil SE Bond or Clearfil Protect Bond/Clearfil AP-X). The volunteers dropped 20% sucrose solution 8x/day and used fluoridated dentifrice 3x/day. After 14 days, enamel mineral loss was assessed by cross-sectional microhardness (CSMH), and the demineralization areas in enamel adjacent to the restoration were examined by scanning electron microscopy (SEM) and polarizing light microscopy (PLM). The CSMH data were analyzed using ANOVA and Tukey's test (p 0.05). Results: Enamel blocks restored with Clearfil Protect Bond showed higher mineral content (%vol) adjacent to restorations than Clearfil SE Bond only for the first site of microhardness measurement and close to enamel surface (20 µm). SEM and PLM analysis suggested that the Clearfil Protect Bond adhesive promoted less enamel demineralization around restorations. Conclusion: After 14 days of cariogenic challenge, the findings suggested that Clearfil Protect Bond might help to control the demineralization around restorations in cases of high caries risk. Keywords: adhesive systems, enamel, microhardness, microscopy