Background: Class ll sandwich restorations are routinely performed where conventional Glass ionomer cement (GIC) or Resin-modified GIC (RMGIC) is used as a base or dentin substitute and a light curing composite resin restorative material is used as an enamel substitute. Various authors have evaluated the microleakage of composite resin restorations where glass ionomer cement has been used as a base in class II sandwich restorations, but a literature survey reveals limited studies on the microleakage analysis of similar restorations with biodentine as a dentin substitute, as an alternative to glass ionomer cement. The aim of this study is: To evaluate the marginal sealing efficacy of a new calcium-silicate-based material (Biodentine) as a dentin substitute, at the cervical margins, in posterior class II sandwich restorations.To compare and evaluate the microleakage at the biodentine/composite interface with the microleakage at the resin-modified GIC/composite interface, in posterior class II open sandwich restorations. To compare the efficacy between a water-based etch and rinse adhesive (Scotch bond multipurpose) and an acetone-based etch and rinse adhesive (Prime and bond NT), when bonding biodentine to the composite. To evaluate the enamel, dentin, and interfacial microleakage at the composite and biodentine/RMGIC interfaces. Materials and Methods: Fifty class II cavities were prepared on the mesial and distal surfaces of 25 extracted human maxillary third molars, which were randomly divided into five groups of ten cavities each: (G1) Biodentine group, (G2) Fuji II LC GIC group, (G3) Biodentine as a base + prime and bond NT + Tetric N-Ceram composite, (G4) Biodentine + scotchbond multi-purpose + Tetric N-Ceram composite, (G5) Fuji II LC as a base + prime and bond NT+ Tetric-N Ceram composite. The samples were then subjected to thermocycling, 2500× (5°C to 55°C), followed by the dye penetration test. Scores are given from 0 to 3 based on the depth of penetration of the dye at the cervical, dentin, and interfacial surfaces. The data was analyzed with the nonparametric Kruskal-Wallis and Mann Whitney U test. Results: No statistically significant differences were found between the five groups in the enamel, dentin, and interfacial regions. Conclusion: Within the limits of this in vitro study, biodentine is a new calcium-silicate-based material, which can be used as a dentin substitute in class II open-sandwich restorations, where its scores better than resin-modified GIC.