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The compatibility of different dental materials (root canal sealer and composite core build-up restoratives) is an important factor for a successful restoration. The aim of this in vitro study was to determine the effects on compressive and diametral tensile strength of a classical chemical cure composite resin (Henry Schein Composite Anterior-Posterior dental restorative) when in contact with either eugenol or an epoxy-resin (EZ-Fill) in a variety of situations: (a) eugenol or epoxy-resin added during mixing of a composite resin before curing; (b) vapor exposure to cured samples; and (c) specimens placed directly in eugenol or epoxy-resin (after curing). Compressive strengths and diametral tensile strengths were tested for each group. Only the addition of eugenol during mixing with the composite resin (directly before curing) resulted in specimens that were unable to be tested, because they did not achieve a full cure or hardness. For all other groups, there were no significant differences with respect to either compressive strength (p = 0.17) or diametral tensile strength (p = 0.39). Group 1 (mixed directly with eugenol) was found to be statistically different from groups 2 through 7.