The purpose of this study was to compare the microleakage and tissue-adhesive interface morphology from Class V restorations using different systems of dentin adhesives. Class V cavities were prepared on buccal surfaces of 27 extracted caries-free molars and premolars. Teeth were randomly assigned to one of three groups: (1) Prime & Bond NT, a 5th generation system using an initial step of total etch followed by a second step of application of a self bonding primer (2) Clearfil SE Bond, a 5th generation adhesive system employing two separate steps of self-etch priming and subsequent bonding (3) One-up Bond F, a 6th generation one step self-etching, self-priming and self-bonding adhesive. Microleakage and interface morphology of teeth restored with these adhesives and a composite resin were evaluated. Kruskal-Wallis Test (p = 0.05) was used to analyze the results. SEM analysis was used to relate interface morphology to microleakage. The mean and (SD) values of microleakage were: Prime and Bond NT: 0.15 (0.33), Clearfil SE Bond: 0.06 (0.17) and One-up Bond F: 2.96 (0.63). The mean microleakage for One-up Bond was significantly higher than for the other groups (p<0.05). Protruding tags in dentin channels were observed in Prime and Bond and Clearfil systems, but not in One-up Bond. The single step adhesive system, although more convenient for the clinician, uses a low viscosity formulation difficult to keep in place on cavity walls. It also tends to be too aggressive and hydrophilic to create an impermeable hybridized tissue-adhesive interfacial layer resistant to microleakage. Two-step adhesive systems, on the other hand, were retained on all segments of the cavosurface during application, and formed a hybridized interfacial layer resistant to microleakage.