Objective: The aim of this prospective, double-blind, randomized long-term study was to evaluate the clinical performance of the self-etch adhesive AdheSE One in combination with the nanohybrid composite resin Tetric Evo Ceram for Class 1 and 2 restorations. The improvement of the clinical performance with the additional use of a flowable composite resin for cavity lining was tested. Method and Materials: In accordance with a split-mouth design, 50 patients received 100 restorations in premolars and molars. One restoration of each patient was chosen at random to be restored with an intermediary layer of a flowable composite resin. Each restoration was scored according to the modified Ryge criteria at baseline and after 6, 12, and 24 months. Results: After 24 months (recall rate 88%), the results of the Ryge evaluation for groups without (group T) and with application (group TF) of Tetric Flow were as follows: marginal adaptation, Alpha 40/40 and Bravo 3/4; marginal discoloration, Alpha 39/41 and Bravo 4/3; and filling integrity, Alpha 42/42 and Bravo 1/2. All restored teeth remained vital. The parameters hypersensitivity, recurrent caries, surface, color match, and proximal contact were scored Alpha for all teeth. Between groups, no statistically significant differences could be detected (Mann-Whitney U test, P > .05). Conclusion: In consideration of the short observation period, the clinical use of AdheSE One in stress-bearing posterior cavities reached acceptable clinical results with a 1.1% cumulative failure rate after 2 years. The use of a flowable composite resin did not show an improved clinical performance. Keywords: clinical study, composite resin, flowable composite, Ryge criteria, self-etch adhesive