Clinical Relevance The application of an extra coat of hydrophobic, solvent-free bonding resin, designed to act as an intermediate flexible layer, was not able to minimize the damage caused by thermal/mechanical load cycling in low C-factor cavities. SUMMARY This study evaluated the influence of adhesive layer thickness (ADL) on the resin-dentin bond strength of two adhesive systems (AS) after thermal and mechanical loading (TML). A flat superficial dentin surface was exposed with 600-grit SiC paper on 40 molars. After primer application, the adhesive layer of Scotchbond Multipurpose (SBMP) or Clearfil SE Bond (CSEB) was applied in one or two layers to a delimited area (52 mm 2 ) and resin blocks (Filtek Z250) were built incrementally. Half of the sample was stored in distilled water (37°C, 24 hours) and submitted to thermal (1,000; 5°-55°C) and mechanical cycles (500,000; 10kgf) [TML]. The other half was stored in distilled water (72 hours). The teeth were then sectioned to obtain sticks (0.8 mm 2 ) to be tested under tensile mode (1.0 mm/minute). The fracture mode was analyzed at 400×. The BS from all sticks from the same tooth was averaged for statistical purposes. The data was analyzed by three-way ANOVA. The χ 2 test was used ( p <0.05) to compare the frequency of pre-testing failure specimens. Higher BS values were observed for SBMP regardless of the ADL. The TML reduced the BS values irrespective of the adhesive employed and the ADL. A higher frequency of pre-testing failure specimens was observed for the cycled groups. A thicker adhesive layer, acting as an intermediate flexible layer, did not minimize the damage caused by thermal/mechanical load cycling for a three-step etch-and-rinse and two-step self-etch system.