Objectives: Due to innumerable confounding factors and a high number of types and brands of dental restorative materials, the clinical performance of restorative materials are sought predicted by various in vitro tests. However, only few such tests have been found to correlate well with clinical findings. Thus, the present study determined the in vitro dentin bond strength and marginal adaptation of Class II restorations and correlated the results to their clinical outcomes. Methods: Dentin bond strength (µTBS and µSBS) and marginal gap formation of Class II restorations (replica technique and SEM) were measured after 24 h and 6 m water storage using eight combinations of adhesive and resin composite. Clinical outcomes (mean survival time, Hazard Ratio, annual failure rate; n = 10.695) were gained from a data set of a retrospective multicenter study of direct restorations. Results: Significant differences were found for dentin bond strength and marginal gap formation between the restorative material groups, and negative effects of long-term storage were observed. µTBS correlated significantly with certain clinical outcomes of Class I restorations, while µSBS correlated with certain clinical outcomes of Class II, III, IV and V restorations. Marginal gap formation in enamel and number of paramarginal fractures correlated with certain clinical outcomes of Class II restorations. Significance: Using the same restorative materials in vitro as in vivo, gave significant, but weak correlations between in vitro bond strength or marginal adaptation and clinical outcomes, lending support to the use of in vitro tests in early stages of material selection.