This study evaluated the clinical outcome of CAD/CAM zirconia-ceramic resin-bonded fixed dental prostheses (RBFDPs) with a cantilevered single-retainer design. Thirty anterior zirconia-ceramic RBFDPs fabricated with the Cerec CAD/CAM system were inserted using either a phosphate monomer containing resin (Panavia 21 TC; N = 16) or an adhesive bonding system with a phosphoric acid acrylate primer (Multilink-Automix with Metal/Zirconia primer; N = 14). During a mean observation time of 64.2 months, one debonding occurred in each group. Both RBFDPs could be rebonded successfully resulting in a five-year survival rate of 100%. Independent of the bonding system, cantilevered zirconia-ceramic RBFDPs showed promising results during the first five years. (ClinicalTrials.gov Identifier: NCT01411592). Single-retainer zirconia ceramic RBFDPs present an alternative treatment option offering good esthetics, a minimally invasive preparation, a high biocompatibility and can even be used to treat juvenile patients who do not yet come into consideration for implant placement. No significant influence of the bonding system used has been detected so far.