Purpose: To evaluate the effect of enzyme-based (Papacárie) and sodium-hypochlorite-based (Carisolv) chemomechanical caries removal methods on bonding of self-etching adhesives to caries-affected dentin, in comparison to the standard rotary-instrument caries removal method. Materials and Methods: Seventy-eight carious permanent molars exhibiting frank cavitation into dentin were used. Forty-eight teeth were randomly divided into three groups, according to the caries excavation methods: (i) Papacárie, (ii) Carisolv and (iii) a round steel bur. After caries removal, each group was subdivided into two groups for two-step (Clearfil SE Bond) or one-step (Clearfil S3 Bond) self-etching adhesive application and resin composite buildups. Bonded specimens were sectioned into beams for microtensile bond strength testing. Bond strength data were analyzed using three-way ANOVA and Tukey's test. For interfacial nanoleakage evaluation using a field-emission scanning electron microscope, caries was similarly removed from the remaining thirty carious molars, bonding was performed as for bond strength testing, and the teeth were sectioned. Results: Results of three-way ANOVA revealed that bond strength was significantly affected by "adhesive" (p 0.001) and "dentin" (p 0.001), but not "caries excavation methods" (p > 0.05). The bond strength of the two-step self-etching adhesive was significantly higher than that of the one-step self-etching adhesive (p 0.001). Conversely, the bond strength of self-etching adhesives to sound dentin was significantly higher than to residual caries-affected dentin (p 0.001). Greater silver penetration was observed in the bonded interfaces of residual caries-affected dentin and in interfaces bonded with the one-step self-etching adhesive vs those bonded with the two-step self-etching adhesive. Conclusion: Chemomechanical caries removal did not affect the bonding of self-etching adhesives to cariesaffected dentin as compared to caries excavation with rotary instruments. Keywords: chemomechanical caries removal, Carisolv, MDP, Papacárie, self-etching adhesives, caries-affected dentin