This study evaluated the enamel-resin interface of three adhesive resins (ARs) by a transmission electron microscope (TEM) after milling with focused ion beam (FIB). Simple Class-I cavities (0.5 mm within enamel depth, 4 mm length, and 2 mm width) were prepared on human caries-free molars. The enamel of two groups was conditioned by one-step self-etch bonding system (Scotchbond((TM))/Single Bond Universal [SBU], and Xeno V (R)+ [XV+]), while the enamel of the third group was etched by phosphoric acid, and then treated by two-step self-priming etch-rinse system (Prime&Bond(®) NT [PBNT]). The application of the adhesive systems was carried out according to their respective manufacturer's instructions. The cavities were restored by a nanofill resin composite (Filtek((TM)) Z350 XT Universal; 3 M ESPE) in one bulk-fill, and cured for 40 s at 550 mW/cm(2) by a halogen light (Optilux 501, Demetron/Kerr, Danbury, USA). The specimens were milled by FIB into 100 nm thickness slices, and then observed under TEM. The transmission electron micrographs showed an adequate adhesion of both two-step etch-rinse (PBNT) and one-step self-etch (SBU) to enamel surface. The deeply etched enamel prisms were impregnated by the etch-rinse PBNT adhesive. A relatively inadequate adhesion associated with some areas of bond degradation underneath the hybrid layer and within the adhesive was noted for the XV+ AR. Apart from the mild acidic adhesives of one-step self-etch and two-step etch-rinse investigated, the highly hydrophilic and acidic water-based one-step self-etch adhesive (XV+) proved to be less effective enamel bond by ultra-structural characterization technique using FIB-TEM.