Purpose: To assess the one-step self-etching adhesive iBond Gluma inside (1-SE) and the two-step etch-andrinse adhesive Gluma Comfort Bond (2-ER), both used in combination with the fine particle hybrid composite Venus, in a laboratory and in a prospective clinical study. Materials and Methods: In the in vitro study, tooth-composite interaction, microleakage, and adhesive failure of 8 Class V restorations per system were evaluated by light and scanning electron microscopy. In the in vivo study, 90 paired Class III/IV restorations were scored over 48 months (modified USPHS criteria). Cumulative failure rates (CFR) were calculated. Results: In vitro, microleakage and adhesive failure at enamel margins were significantly increased with 1-SE in comparison with 2-ER. With 1-SE, micromechanical interlocking at enamel was reduced and pores within the adhesive layer arose. In vivo, after 48 months with 1-SE, decreased marginal integrity and an increased number of dark marginal color lines were observed. Conclusion: Because the results of the 4-year clinical study showed lower esthetics and marginal integrity for the 1-SE adhesive, its use should be viewed critically, which is in line with the reduced enamel-adhesive-composite interaction found in vitro. Schlagwörter: dental adhesive, composite, in vitro test, tooth-composite interface, in vivo test