This study was carried on to assess the clinical performance of a novel restorative concept consisting in single monolithic lithium disilicate full-contour crowns bonded on computer-aided design/computer-aided manufacturing (CAD/CAM) zirconia complete-arch implant bridges, to overcome the drawbacks related to the chipping of porcelain fused to zirconia restorations. Sixteen patients received 18 implant-supported hybrid screw-cement-retained complete-arch restorations, consisting of single monolithic lithium disilicate full-contour crowns bonded on CAD/CAM zirconia frameworks. The restorations were supported by 4-8 implants. All patients were followed up for at least 3 years on function (range 36 to 60 months, mean 49.3 months). Clinical controls were scheduled every 4 months. The outcomes were implant and prosthetic survival and success rates, any complications, patient satisfaction, and soft tissue parameters. No dropouts occurred. The overall implant and prosthesis survival rates were 100%. One of 18 restorations (1 of 236 dental units) showed a chip-off fracture of the veneering ceramic that was polished intraorally without any additional treatment, scoring a cumulative prosthetic success rate of 100%, according to the California Dental Association index. All patients were functionally and esthetically highly satisfied with their restorations. Successful soft tissue parameters were found around all implants. Single monolithic lithium disilicate full-contour crowns, bonded on CAD/CAM screw-retained complete-arch zirconia frameworks, showed favorable preliminary outcomes with medium-term follow-up. However, randomized controlled studies of this technique are required for further conclusive recommendations.