Fracture resistance of inlays and onlays may be influenced by the quantity of the dental structure removed and the restorative materials used. The purpose of this in vitro study was to evaluate the effects of two different cavity preparation designs and all-ceramic restorative materials on the fracture resistance of the tooth-restoration complex. Fifty mandibular third molar teeth were randomly divided into the following five groups: group 1: intact teeth (control); group 2: inlay preparations, lithium-disilicate glass-ceramic (IPS e.max Press, Ivoclar Vivadent AG, Schaan, Liechtenstein); group 3: inlay preparations, zirconia ceramic (ICE Zirkon, Zirkonzahn SRL, Gais, Italy); group 4: onlay preparations, lithium-disilicate glass-ceramic (IPS e.max Press); and group 5: onlay preparations, zirconia ceramic (ICE Zirkon). The inlay and onlay restorations were adhesively cemented with dual polymerizing resin cement (Variolink II, Ivoclar Vivadent AG). After thermal cycling (5 degrees to 55 degrees C x 5000 cycles), specimens were subjected to a compressive load until fracture at a crosshead speed of 0.5 mm/min. Statistical analyses were performed using one-way analysis of variance and Tukey HSD tests. The fracture strength values were significantly higher in the inlay group (2646.7 +/- 360.4) restored with lithium-disilicate glass-ceramic than those of the onlay group (1673.6 +/- 677) restored with lithium-disilicate glass-ceramic. The fracture strength values of teeth restored with inlays using zirconia ceramic (2849 +/- 328) and onlays with zirconia ceramic (2796.3 +/- 337.3) were similar to those of the intact teeth (2905.3 +/- 398.8). In the IPS e.max Press groups, as the preparation amount was increased (from inlay to onlay preparation), the fracture resistance was decreased. In the ICE Zirkon ceramic groups, the preparation type did not affect the fracture resistance results.