The purpose of this in vitro study was to compare the quasi-static load-bearing capacity of all-ceramic resin-bonded three-unit inlay-retained fixed dental prostheses (IRFDPs) made from computer-aided design/computer-aided manufacturing (CAD/CAM)-manufactured yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) frameworks with two different connector dimensions, with and without fatigue loading. Twelve IRFDPs each were made with connector dimensions 3 x 3 mm(2) (width x height) (control group) and 3 x 2 mm(2) (test group). Inlay-retained fixed dental prostheses were adhesively cemented on identical metal-models using composite resin cement. Subgroups of six specimens each were fatigued with maximal 1,200,000 loading cycles in a chewing simulator with a weight load of 25 kg and a load frequency of 1.5 Hz. The load-bearing capacity was tested in a universal testing machine for IRFDPs without fatigue loading and for IRFDPs that had not already fractured during fatigue loading. During fatigue testing one IRFDP (17%) of the test group failed. Under both loading conditions, IRFDPs of the control group exhibited statistically significantly higher load-bearing capacities than the test group. Fatigue loading reduced the load-bearing capacity in both groups. Considering the maximum chewing forces in the molar region, it seems possible to use zirconia ceramic as a core material for IRFDPs with a minimum connector dimension of 9 mm(2). A further reduction of the connector dimensions to 6 mm(2) results in a significant reduction of the load-bearing capacity.