Purpose: To evaluate the bond strength on different cavity walls of Class II preparations. Different bonding systems and the effect of thermomechanical cycling were investigated. Materials and Methods: Human third molars received MOD preparations with dentin margins. Teeth were randomly assigned to 18 groups (n = 5) according to the combination of cavity wall (axial, occlusal, and gingival), bonding system (Single Bond Plus, Clearfil SE Bond, and Adper Prompt) and the occurrence of thermomechanical cycling. Restorations were concluded with Filtek Z250 composite. Specimens were sectioned according to the respective cavity wall (4 slabs/restoration), and the adhesive interface was trimmed to an hourglass shape (1 mm2). Slabs were tested under tension, and failure mode was observed. Bond strength data were analyzed with three-way ANOVA/Tukey's test. Results: Single Bond Plus and Clearfil SE Bond performed similarly under most experimental conditions. Single Bond Plus presented similar bond strength on the three cavity walls, regardless of the aging condition. Clearfil SE Bond exhibited significant differences among cavity walls: the occlusal wall showed higher means in both aging conditions. Non-aged gingival walls and aged axial and gingival walls yielded lower means. Non-aged Adper Prompt produced similar bond strengths on the three cavity walls. After thermomechanical cycling, the gingival wall showed lower means. Conclusion: The effect of cavity walls was dependent on the bonding system and thermomechanical cycling. Adper Prompt demonstrated bond strengths lower than Single Bond Plus or Clearfil SE Bond under most experimental conditions. Keywords: dental adhesion, class II restoration, fatigue, thermal cycling, bond strength testing