Objective The aim of this study is to investigate the microleakage attained with three resin-based material used to restore deep Class II cavities. A null hypothesis was chosen: there is no difference in microleakage among the tested materials. Materials and Methods A total of 30 Class II cavities were prepared in freshly extracted molars with the proximal mesial and distal margins located, respectively, 1.5 mm apically and 1.5 mm coronally to the cementum-enamel junction. Restorations were completed using a three-step enamel-dentin adhesive system “Etch and Rinse,” margins were relocated using a micro-hybrid, preheated, or flowable composite and restorations were then completed using a conventional composite. All samples were coated with nail varnish with the exception of an area along the margins and apex was sealed using epoxide cement and then thermocycled (30-s dwell time, 5°C/55°C, 1000 cycles). A 50% ammoniac AgNO3 solution was used as tracer according to Tay’s protocol. The microleakage analysis was performed using a microtomography system Sky-scan 1072 (SKYSCAN, Kartuizersweg 3B 2550, Konitch, Belgium). Results The mean microleakage of all the tested materials showed greater leakage in the cementum margins; flowable composite exhibit greater leakage among the groups. Significant differences (P textless 5%) within groups in both enamel and dentin margins were present. None of the tested materials eliminated marginal microleakage. Preheated composite showed significantly lesser microleakage. Conclusion Tested materials showed statistical differences in microleakage; thus, the null hypothesis has been rejected. Within the limitations of the present experimental procedure, it can be concluded that flowable resin composite should be avoided at the dentin/cementum margin.