OBJECTIVE Evaluation of the fracture resistance of all-ceramic cantilever fixed dental prostheses (FDPs) manufactured from zirconia frameworks and veneered with a press ceramic. METHODS Two mandibular premolars were prepared either with a box inlay cavity or with a full crown chamfer preparation and then duplicated. 40-three-unit cantilever FDPs replacing one premolar, with a group size of eight for each design, were manufactured. In group i-i the cantilever FDPs were retained by two inlays, in group i-c by an inlay-crown combination, and in group c-c by two crowns. The frameworks in groups i-c-R and c-c-R were reinforced by an additional shoulder on the oral side of the zirconia frameworks. All FDPs were subjected to thermal cycling (TC) and 600,000 cycles of mechanical loading (ML) with 50 N. The load to fracture was measured and fracture sites were evaluated. RESULTS The mean fracture values ranged from 172 N to 792 N. Fracture-strength values were significantly lower for the i-i retained FDPs than for the i-c and c-c combinations. There was no significant effect of the reinforcing shoulder in groups i-c-R and c-c-R. For FDPs with a crown on the terminal tooth, fractures were usually within the distal wall of the distal crown. CONCLUSIONS Inlay-inlay retained cantilever FDPs cannot withstand the mastication forces expected. Fracture load values for inlay-crown and crown-crown-retained FDPs encourage further clinical investigation. The mode of fracture indicates that reinforcement of the distal crown wall might enhance fracture resistance.