Functional monomers chemically interact with hydroxyapatite that remains within submicron hybrid layers produced by mild self-etch adhesives. The functional monomer 10-MDP interacts most intensively with hydroxyapatite, and its calcium salt appeared most hydrolytically stable, as compared with 4-MET and phenyl-P. We investigated the hypothesis that additional chemical interaction of self-etch adhesives improves bond stability. The micro-tensile bond strength (muTBS) of the 10-MDP-based adhesive did not decrease significantly after 100,000 cycles, but did after 50,000 and 30,000 cycles, respectively, for the 4-MET-based and the phenyl-P-based adhesives. Likewise, the interfacial ultrastructure was unchanged after 100,000 thermocycles for the 10-MDP-based adhesive, while that of both the 4-MET- and phenyl-P-based adhesives contained voids and less-defined collagen. The findings of this study support the concept that long-term durability of adhesive-dentin bonds depends on the chemical bonding potential of the functional monomer.