The aim of this study was to evaluate the marginal adaptation of CEREC ceramic inlays, CEREC composite inlays and direct composite restorations in unbeveled proximal slot cavities under artificial aging conditions. Two groups of each restoration type were prepared (n = 6), one group with a self-etch adhesive, the other group with H3PO4 enamel etching before the self-etch adhesive application. Replicas were generated before and after long-term thermo-mechanical loading under dentinal fluid simulation and margins were evaluated at ×200 magnification in the scanning electron miscroscope (SEM). Statistically, significant differences were found before and after loading with respect to the percentages of “continuous margins”, the direct composite filling with H3PO4 enamel etching giving the lowest percentages of “continuous margins” after loading (p < 0.05). The highest percentage of “continuous margin” was attained by composite inlays without H3PO4 enamel etching. However, these results were not significantly different from ceramic inlays after stressing. Polymerization shrinkage is still one critical property of composite restorative materials. The marginal adaptation of indirect adhesive proximal slot restorations without enamel bevels both fabricated out of composite and ceramic is better than that of directly placed composite restorations.