Objective: The purpose of this study was to evaluate the effect of different caries removal techniques on the bond strength of two adhesive systems. Materials and Methods: Seventy human molar teeth that had proximal carious lesions were randomly divided into four groups according to the technique used to remove the caries: a conventional steel bur, an Er:YAG laser, a chemomechanical Carisolv((R)) gel, and air polishing. The groups were then divided into two subgroups according to the adhesives used: Clearfil S-3 (Kuraray Co., Ltd, Tokyo, Japan) and Adper SE Plus (3M ESPE, St Paul, MN, USA). The enamel and superficial dentin of the crown was flattened and caries were removed using different methods. Teeth were restored with composite and three 1mm(2) stick-shaped microtensile specimens were prepared from each tooth. For each removal technique, the surface roughness of one dentin sample was analyzed using atomic force microscopy (AFM). The microtensile bond strength data were then analyzed using a two-way ANOVA, Kruskal-Wallis and Mann-Whitney U tests, and multiple comparison tests (p=0.05). Results: The two-way ANOVA showed that the effects of the cavity preparation techniques and adhesive systems and their interaction were statistically significant (p<0.05). The TBS values were highest when bonding with Adper SE Plus to cavities prepared with the steel bur (37.20 +/- 11.65MPa) and lowest when bonding with Clearfil S-3 Bond to cavities prepared with the Er:YAG laser (16.74 +/- 6.95MPa). Conclusion: The caries removal techniques affected the bond strength values of the self-etch adhesive systems.