Laboratory testing of dentin adhesive systems still requires corroboration by long-term clinical trials for their ultimate clinical effectiveness to be validated. The objective of this clinical investigation was to evaluate, retrospectively, the clinical effectiveness of earlier-investigated dentin adhesive systems (Scotchbond, Gluma, Clearfil New Bond, Scotchbond 2, Tenure, and Tripton), and to compare their clinical results with those obtained with four modern total-etch adhesive systems (Bayer exp. 1 and 2, Clearfil Liner Bond System, and Scotchbond Multi-Purpose). In total, 1177 Class V cervical lesions in the teeth of 346 patients were restored following two cavity designs: In Group A, enamel was neither beveled nor intentionally etched, as per ADA guidelines; in Group B, adjacent enamel was beveled and conditioned. Clinical retention rates definitely indicated the improved clinical efficacy of the newest dentin adhesives over the earlier systems. With regard to adhesion strategy, adhesive systems that removed the smear layer and concurrently demineralized the dentin surface layer performed clinically better than systems that modified the disorderly layer of smear debris without complete removal. Hybridization by resin interdiffusion into the exposed dentinal collagen layer, combined with attachment of resin tags into the opened dentin tubules, appeared to be essential for reliable dentin bonding but might be insufficient by itself. The additional formation of an elastic bonding area as a polymerization shrinkage absorber and the use of a microfine restorative composite apparently guaranteed an efficient clinical result. The perfect one-year retention recorded for Clearfil Liner Bond System and Scotchbond Multi-Purpose must be confirmed at later recalls.