Clinical Relevance Using a material that optimizes marginal seal when using a margin elevation technique to manage deep class II cavities should enhance clinical outcomes. SUMMARY Objectives: The purpose of this laboratory study was to perform a tridimensional interfacial gap evaluation of class II cavities with enamel and dentin cervical margins, before and after cyclic fatigue, restored with different nanohybrid resin composites. Methods and Materials: Standardized class II cavities were performed on 48 intact maxillary premolars, placing the mesial cervical margin 1 mm above the cement–enamel junction (CEJ) and the distal cervical margin 1 mm below the CEJ. Specimens were treated with two-step self-etch adhesive (Clearfil SE Bond2) and divided into six groups according to the restoration technique. Microcomputed Tomography imaging was executed before and after 1,000,000 cycles of chewing simulation at 50 N. Tridimensional interfacial gaps, expressed as cubic millimeters, were analyzed through a standardized software flowchart (Mimics). Data were analyzed with a two-way analysis of variance and Tukey post hoc tests (α=0.05). Results: Restoration technique ( p =0.001) and chewing simulation ( p =0.00001) significantly influenced interfacial gap on dentin but not on enamel. The post hoc test showed that, on dentin margins, flowable resins had a lower gap at baseline but a higher gap after chewing simulation, especially when a 2-mm-thick layer was applied, compared with nanohybrid and bulk-fill composites. Conclusions: Based on the obtained results, no differences in interfacial gap volume were found on enamel margins. On dentin margins, flowable resins showed better marginal seal at baseline, but they seem to be more prone to interfacial degradation during chewing simulation than traditional composites.