OBJECTIVE To determine the influence of thermal and mechanical cycling on fracture load and fracture pattern of resin nanoceramic crowns and polymer-infiltrated ceramic-network (PICN) crowns, both fabricated with CAD/CAM technology. METHODS A total of 90 premolar crowns bonded to titanium abutments were divided into three groups of 30 crowns each: 30 resin nanoceramic crowns (LU); 30 PICN crowns (VE); and 30 metal-ceramic crowns (MC). The 30 specimens of each group were further divided into three subgroups of 10 each that underwent (1) no treatment, (2) thermocycling (2,000 cycles, 5°C to 55°C), and (3) thermocycling with subsequent mechanical cycling (120,000 cycles, 80 N, 2 Hz). The specimens were loaded to failure, and two-way ANOVA and chi-square test were used to determine differences in fracture resistance and pattern. RESULTS Mechanical and thermal cycling significantly influenced the critical load to failure of the three materials; however, no significant differences were observed between the thermocycled materials and the materials that were thermocycled with subsequent mechanical cycling. The MC specimens experienced significantly higher fracture loads than those of the LU and VE specimens, which showed no differences from each other in fracture resistance. The fracture patterns showed chipping in MC crowns and partial or complete fracture in LU and VE crowns. The fracture pattern depended on the material and was unrelated to the type of treatment it underwent. CONCLUSIONS All crowns showed adequate resistance to normal masticatory forces in the premolar area. The cyclic fatigue load negatively influenced all three materials.