Purpose: To investigate the influence of selective enamel etching on long-term clinical performance of partial ceramic crowns (PCCs) luted with a self-adhesive luting material (RXU: RelyX Unicem). Materials and Methods: At baseline, 34 patients received the intended treatment: two PCCs (Vita Mark II; Cerec 3D) for the restoration of extended lesions with multiple-cusp coverage were placed in a split-mouth design with a self-adhesive luting material, one without (RXU) and one with selective enamel etching (RXU+E). Patients were evaluated clinically (modified USPHS criteria) at baseline and up to 6.5 years (70 to 88 months). The chi-square test was used for statistical analyses (α = 0.05). Clinical survival of all restorations (n = 68) after 6.5 years was evaluated by Kaplan-Meier analysis. Results: After 6.5 years, 18 patients (9 male, 9 female; median age 41, range 25 to 59 years) with 36 RXU and RXU+E restorations were available for clinical assessment (patient recall rate: 53%), with 13 RXU and 14 RXU+E PCCs placed in molars and 5 RXU and 4 RXU+E PCCs in premolars. Clinically, no statistically significant differences between the luting procedures were detected. Both RXU and RXU+E revealed significant changes over time with respect to marginal adaptation (significant deterioration) and marginal discoloration (significant increase). RXU revealed no cases of postoperative hypersensitivity and RXU+E only did so at baseline (n = 5). Kaplan-Meier analysis showed a cumulative survival for RXU of 60% and for RXU+E of 82%, indicating a significantly higher survival rate for RXU+E. Conclusion: Clinically, RXU and RXU+E perform similarly. In PCC restorations with multiple-cusp coverage, lack of retention due to adhesive preparation, and little dentin available for adhesion caused by extensive core buildups or cavity linings, selective enamel etching is recommended. Keywords: partial ceramic crowns, self-adhesive luting materials, selective enamel etching, prospective clinical study