This study compared the degree of microleakage in the proximal walls of direct and indirect resin slot restorations in relation to the types of dentin bonding systems and the location of gingival margins. Two Class II slot preparations were prepared and restored in each of 60 extracted human molars using direct (Filtek Supreme) and indirect (Tescera ATL) restorative resin materials. Various types of dentin bonding systems, including self-etching (OneStep Plus/Tyrian SPE, iBond, Xeno III) and etch and rinse systems (All-Bond 2, Prime & Bond NT) were used to restore the prepared teeth. The gingival proximal wall was placed apical to the cementoenamel junction (CEJ) in 1 proximal box and coronal to the CEJ in the other. The specimens were stained and evaluated for microleakage using a digital imaging and analysis system. Significant differences were found in the degree of microleakage observed in the various restorative groups. In general, the group restored with indirect resin had less microleakage than the direct resin groups. Factors, such as type of dentin bonding system and location of gingival margins, exert a substantial influence on the degree of microleakage that occurred along the walls of proximal resin restorations.