To investigate the sealing ability of the Clearfil Liner Bond 2 self-etching primer in Class V restorations placed under clinical and laboratory conditions.Firstly, the influence of two etching times of the self-etching primer were tested in vitro. In 10 Class V cavities (Group 1), the self-etching primer was applied for 30 seconds on the enamel and dentin, while in another 10 Class V cavities (Group 2) the etching time was 60 seconds. Since the Group 2 samples showed the best in vitro sealing ability at both the enamel and cementum-dentin sites, the teeth of Group 3 (10 restorations) were restored as in Group 2 under clinical conditions, applying the self-etching primer for 60 seconds. The sample teeth were extracted after 65-90 days, and then processed for leakage. Two other groups of 10 samples each were prepared under laboratory conditions to investigate hybrid layer, resin tags and adhesive lateral branch formation. A flat buccal surface on each extracted tooth was prepared. Group 4 samples were conditioned for 30 seconds, and those of Group 5 for 60 seconds.In Group 1, 40% of the restorations showed leakage at the cementum-dentin site and 40% at the enamel site. Groups 2 and 3 showed statistically significant difference (less leakage) than Group 1. In Group 2 and 3 no leakage was found at the enamel site, and only a moderate leakage (10% and 20% of restorations, respectively) was found at the cementum-dentin site. The scanning electron microscopy observations of Group 4 samples showed a thin hybrid layer, with well-fitting and smooth resin tags and adhesive lateral branches only sporadically. Group 5 samples presented a thicker hybrid layer, rough and deep resin tags with many adhesive lateral branches. The etch enamel pattern was more uniform and rougher in Group 5 than in Group 4. The 60-second application time of the self-etching primer seems to be more reliable than a shorter conditioning time in day-to-day practice.