Objective: The purpose of this study was to evaluate the effects of pre- and post-irradiation application on the shear bond strength of self-adhesive luting cements to dentin and enamel. Materials and Methods: Thirty-two extracted human maxillary incisor teeth were used in this study. Teeth were divided into two main groups according to preparation depth (0.5 mm and 1 mm) as Group E and Group D and were divided into four subgroups according to treatment protocol (n = 12). Teeth were irradiated and preparation was done after radiation. Adhesive luting cement was placed on the irradiated enamel and dentin surface (Groups E1, D1). Preparation was done before irradiation and resin cement was placed on the irradiated enamel and dentin surface (Groups E2, D2). The resin cement was first placed on their enamel and dentin surfaces and then the specimens were irradiated (Groups E3, D3). Irradiation was done with a total dose of 60 Gy, applied in fractions over 6 weeks for each groups (2-Gy/day fractions, 5 days per week). Nonirradiated groups were determined as controls groups (Groups C1, C2). The shear bond strengths of adhesive luting cement were examined. Results: According to the two-way ANOVA results, depth of preparation and treatment protocol and their interactions were significant on shear bond strength of resin cement (P < 0.05). Conclusions: This study detected significant differences between the irradiated and nonirradiated groups, probably due to the changes in the crystalline structure of dental hard tissues.