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Despite the excellent esthetics of veneered zirconia crowns, the incidence of chipping and fracture of veneer porcelain on zirconia crowns has been recognized to be higher than in metal ceramic crowns. The objective of this investigation was to study the effect of selected variations in core thickness on the post-fatigue fracture resistance of veneer porcelain on zirconia crowns.Zirconia crowns for veneering were prepared with three thickness designs of (a) uniform 0.6-mm thick core (group A), (b) extra-thick 1.7 mm occlusal core support (group B), and (c) uniform 1.2-mm thick core (group C). The copings were virtually designed and milled by the CAD/CAM technique. Metal ceramic copings (group D) with the same design as in group C were used as controls. A sample size of N = 20 was used for each group. The copings were veneered with compatible porcelain and fatigue tested under a sinusoidal loading regimen. Loading was done with a 200 N maximum force amplitude under Hertzian axial loading conditions at the center of the crowns using a spherical tungsten carbide indenter. After 100,000 fatigue cycles, the crowns were axially loaded to fracture and maximum load levels before fracture was recorded. One-way ANOVA (P < 0.05) and post hoc Tukey tests (α = 0.05) were used to determine significant differences between means.The mean fracture failure load of group B was not significantly different from that of control group D. In contrast, the mean failure loads of groups A and C were significantly lower than that of control group D. Failure patterns also indicated distinct differences in failure mode distributions. The results suggest that proper occlusal core support improves veneer chipping fracture resistance in zirconia crowns.Extra-thick occlusal core support for porcelain veneer may significantly reduce the veneer chipping and fracture of zirconia crowns. This is suggested as an important consideration in the design of copings for zirconia crowns.