This study investigated the effect of loading on the bond strength to dentin and microleakage of MOD indirect composite restorations bonded with self-adhesive and self-etching resin cements with or without acid etching of the proximal enamel margins. Class II MOD cavities were prepared in 48 molar teeth into dentin and divided into three groups of 16 teeth. Impressions were taken and indirect composite inlays fabricated (Estenia C & B). The enamel margins of the proximal boxes of half the specimens were phosphoric acid etched, and the inlays were cemented with one of three cements (Panavia F 2.0, SA Cement, or Rely X Unicem). After luting, eight teeth in each cement group were mechanically loaded at 2.5 cycles/s for 250,000 cycles. Unloaded teeth acted as controls. Teeth were stored in Rhodamine B solution for 24 hours, sectioned buccolingually at the proximal boxes to examine microleakage using confocal microscopy, and further sectioned for μTBS testing of the resin-dentin interface. Analysis of variance was performed to assess the effect of loading and acid etching on microleakage and bond strength. Acid etching had no effect on microleakage. No significant difference in the dentin bond strengths between the three cements existed after loading. Panavia F 2.0 exhibited a significant reduction in bond strength. With regard to microleakage at the proximal boxes, loading had no effect on dye penetration at the cavity floor. However, at the axial walls, loading had a significant deleterious effect on Panavia F 2.0. No difference in microleakage existed between the three cements at both sites before and after loading. In conclusion, the two tested self-adhesive cements exhibited similar bond strengths before and after loading to the self-etching resin cement. Loading reduced dentin bond strengths and increased microleakage at the resin-dentin interface. However, acid etching of the enamel margins had no significant effect on microleakage in the approximal regions of the bonded inlays.