The purpose of this study was to compare the reactivity of three dentifrice formulations on smear layer-covered root dentin surfaces, and the effects of the formulation treatments on resistance to acid softening and dentinal tubuli disclosure. Commercial dentifrices, including Crest Cavity Protection Regular, Colgate Total, and a new dentifrice comprised of stannous fluoride/sodium hexametaphosphate (SnF2/HMP: Crest Pro-Health), were cycled through a pre-treatment period on smear layer-covered dentin surfaces, including intermittent soaking in dentifrice slurries and whole human saliva immersion. Following pre-treatments, the cycling treatments were modified to include dietary acid exposure, including soaks in an acidic soft drink. Vickers surface microhardness, variable pressure scanning electron microscopy (VP-SEM), and confocal laser scanning microscopy in reflection mode (CLSM) were used to characterize dentin reactivity and smear layer protection. CLSM and SEM analyses showed that specimens treated with SnF2/HMP appeared to resist acid solubilization, evidenced by the absence of disclosed dentinal tubuli. The histo-tomographic observations in this study were in agreement with the hardness measurements. The superior surface protection of dentin with SnF2/HMP would suggest potential benefits in ameliorating dentinal hypersensitivity in the clinical situation. A stannous fluoride/sodium hexametaphosphate dentifrice prevents dietary acid softening and tubule exposure of smear layer dentin surfaces.