The importance of the Dentin Enamel Junction (DEJ) to the durability of adhesive bonds to tooth structure is unclear. In fact, no investigation has been reported on contributions of the DEJ to the fatigue resistance of the bonded interface. In this study, the durability of adhesive bonds to tooth structure involving the DEJ was quantified and compared to that of adhesive bonds to enamel only, not including the DEJ. Two different configurations of enamel bonding were considered, including when tensile stress is focused on the outer enamel (occlusal configuration) or the inner decussated enamel (decussated configuration). The resistance to failure for all bonded interfaces was assessed under both static and cyclic loading to failure. Results showed that the durability of the bonded interfaces was primarily a function of their resistance to crack initiation and growth. The bonded interface strength involving the DEJ was significantly (p ≤ 0.05) greater than that of bonds to enamel only with occlusal configuration, under both static and cyclic loading. While the fatigue strength of bonds involving the DEJ was approximately 20% greater than that for enamel bonds with occlusal configuration (7.7MPa) it was lower than that of enamel with the decussated configuration. The DEJ deterred cracks from extending readily into the dentin but it did not prevent fatigue failure. These results suggest that the durability of bonds to enamel are most dependent on the enamel rod decussation and that the DEJ plays a minor role.