Objective: To evaluate the microleakage of three self-adhesive cements and one etch & rinse resin cement on dentin and enamel interfaces. Methods: 48 inlays preparations (n=12) with enamel and dentin margins were performed on extracted teeth. After impressions, indirect composite inlays were manufactured and luted with self-adhesive resin cements (RelyX U100, Maxcem or SpeedCem) or an etch & rinse resin cement (Nexus 3). Restored teeth were thermocycled and immersed in a silver nitrate solution. Specimens were cut through restorations, surfaces were photographed and microleakage was measured with aid of computer software (Image J). Statistical analysis was realized with Kruskal-Wallis nonparametric test (P<0.05). Results: Statistical analysis of enamel-cement interfaces showed that Nexus provided better marginal sealing than Speedcem (p<0.05). Considering dentin-cement interface, RelyX U100 presented the smaller microleakage degree than Speedcem and Maxcem (p<0.05). Conclusions: Among self-adhesive resin cements, RelyX U100 showed better sealing ability of enamel and dentin margins and its performance was comparable to Nexus 3.