Purpose: To evaluate the effect of smear-layer interposition on the bonding effectiveness of self-etching adhesives with different etching potential. Materials and Methods: Bur-cut dentin specimens were obtained from 25 human molars after preparation of the dentin surface with a medium-grit diamond bur (bur-cut). An additional 25 molars were fractured at the midcoronal dentin to create a smear-layer-free surface (smear-free dentin). The prepared teeth were assigned to 5 groups, according to the adhesive to be applied: a strong one-step self-etching adhesive (PLP, Adper Prompt L-Pop, 3M ESPE, pH = 0.8); two ultra-mild one-step self-etching adhesives (C3S, Clearfil Tri-S Bond, Kuraray, pH = 2.7; AEB, Adper Easy Bond, 3M ESPE; pH = 2.7 ); as the self-etching control, a mild two-step self-etching adhesive (CSE, Clearfil SE Bond, Kuraray, pH of primer = 1.9); and as the etch-and-rinse control, a three-step etch-and-rinse adhesive (OFL, Optibond FL, Kerr). After composite buildups were made, all specimens were stored in distilled water (24 h/37°C) prior to microtensile bond strength testing (µTBS). The failure mode was determined with a stereomicroscope at 50X magnification. Representative µTBS specimens were processed for analysis in a Feg-SEM. The Kruskal-Wallis test was performed to determine statistical differences (p 0.05). Results: Except for the strong one-step self-etching adhesive, all other self-etching adhesives (mild and ultramild) revealed a significantly lower bond strength to bur-cut dentin than to smear-free dentin. The etch-and-rinse adhesive presented the highest µTBS, which was not significantly different when bonded to bur-cut or smear-free dentin. Fracture analysis demonstrated a prevalence of adhesive failures for the self-etching adhesives, while OFL revealed more mixed failures. SEM revealed that smear debris remained part of the adhesive interfacial complex produced by the ultra-mild one-step self-etching adhesive C3S when applied on bur-cut dentin. Conclusion: Smear debris interferes with the interaction of mild and ultra-mild self-etching adhesives with dentin. Keywords: dentin bonding, smear layer, etch-and-rinse adhesive, self-etching adhesive, etching potential