Objective: The aim of this randomized multicenter clinical trial was to evaluate and compare the performance of anterior all-ceramic implant crowns based either on prefabricated zirconia abutments veneered with pressed ceramics or on CAD/CAM zirconia abutments veneered with the hand build-up technique. The null hypothesis was that there is no statistically significant difference between the two study groups. Material and methods: Forty implants were inserted in sites 14–24 (World Dental Federation [FDI]) in two centers, the Universities of Bern and Geneva, Switzerland. Twenty patients each were randomized into either Group A and restored with one-piece single crown made of a prefabricated zirconia abutment with pressed ceramic, or Group B using an individualized CAD/CAM zirconia abutment with the hand-layered technique. After 3 years, clinical, esthetic, and radiographic parameters were assessed. Results: Group A exhibited one dropout patient and one failure resulting in a survival rate of 89% after 3 years and two failures for Group B (90%). Clinical parameters presented healthy peri-implant soft tissues. Overall, no crestal bone level changes were observed (mean DIB of 0.13 mm [Group A] and 0.24 mm [Group B]). There were no significant differences at baseline, 6 months, and 1 and 3 years for DIB values between the two groups. PES and WES values evaluated at all three time points indicated stability over time for both groups and pleasing esthetic outcomes. Conclusions: Both implant-supported prosthetic pathways represent a valuable treatment option for the restoration of implant crowns in the anterior maxilla.