Purpose: The aim of this study was to evaluate, in a case control study, the esthetic and functional clinical performance of ceramic inlays used for covering the screw access hole in single monolithic lithium disilicate full-contour crowns bonded on computer-aided design/computer-aided manufacturing (CAD/CAM) prefabricated titanium abutments in order to eliminate the drawbacks of alternative restorative methods. Materials and Methods: Twenty-eight patients with missing teeth in the lateral areas (premolars and molars) received screw-retained implant restorations. In half of the restorations (n = 14), composite fillings were used to seal the access hole (control group), while the other half was sealed with ceramic inlays (test group). To determine the restoration occlusal wear, impressions were obtained after the restorations were finalized, at 1 year, and at 2 years follow-up. The casts were scanned with a 3D Scanner Design System recording the anatomical surfaces of the white model replicates. Wear amounts (μm) were calculated as the maximum loss in height of the occlusal surface. The clinical evaluation was carried out using a kit specifically designed for assessing the FDI criteria. Statistics were performed using analysis of variance (ANOVA). Results: A total of 58 restorations were delivered, and after 2 years of follow-up, the wear values were 228.20 ± 54.68 μm for the control group and 65.20 ± 7.24 μm for the ceramic inlay group. One-way ANOVA showed significant differences among the vertical loss between these two groups (P .001). Clinical outcomes according to the FDI score for assessing dental restorations revealed substantial deterioration within 2 years of follow-up. Conclusion: The use of ceramic inlays appears to be a predictable, esthetic, and successful method of sealing the screw holes of the screw-retained implant restorations. Keywords: composite resins, esthetics, implant-supported dental prostheses, inlays, restoration occlusal wear, screw