Purpose: To evaluate the resistance to fracture in cantilevered fixed dental prostheses (cFDPs) of single implant-supported zirconia cantilevers in the anterior region. Materials and Methods: Thirty-two cemented and solely screw-retained cFDPs consisting of an implant-supported crown replacing the central incisor and an attached cantilever unit in the position of the lateral incisor in the maxilla were constructed by computer-aided design (CAD) and machined by computer-aided manufacturing (CAM). For the cemented solution, a cFDP was designed on top of a customized abutment luted to an adhesive base. For screw-retained cFDPs, abutment, cement gap, and restoration of the cementable design were combined. All cFDPs were veneered manually on the facial side. Half of the samples underwent artificial aging (thermocycling and chewing simulation) before fracture tests were conducted with loads applied to the pontic either parallel to the implant axis (axial loading on the pontic) or tilted lingually by α = 45 degrees (oblique loading on the pontic). Thus, there were eight groups differing in cFDP design, artificial aging, and load application (n = 8/group). If fracture (F_u,total) occurred within the implant components, the adhesive base was replaced by a cast CoCr base, and the cFDP's fracture resistance (F_u,cFDP) was also determined. Using statistical analyses (SPSS 24, IBM), factors affecting fracture resistance were identified. Results: F_u,total was mainly correlated to screw fractures and therefore not affected by cFDP design. Oblique loading on the pontic (F_u,total = 231 N - 352 N), however, led to a significant (P .001) decrease in ultimate load compared with axial loading on the pontic (F_u,total = 611 N - 815 N). In relation to F_u,total, F_u,cFDP was approximately twice as high for both loading conditions. Conclusion: When relating the results to maximum occlusal forces exerted in the maxillary anterior region, single implant-supported cFDPs can be a viable restorative treatment option. Keywords: CAD/CAM, extension bridge, fracture load, implant-supported, zirconia