Purpose: To investigate the effects of different commercially available computer-aided design/computerassisted manufacturing (CAD/CAM) materials for fabrication of molar crowns, including polyetheretherketone (PEEK), on the fracture strength and failure mode of custom-made titanium and zirconia abutments after artificial aging. Materials and Methods: A total of 48 identical custom-made CAD/CAM abutments milled out of titanium or zirconia were divided into six test groups of eight specimens each. The groups were assigned as follows: titanium abutments restored with zirconia crowns (TiZ), with lithium disilicate crowns (TiL), or with PEEK crowns (TiP); zirconia abutments bonded to a titanium base and restored with zirconia crowns (ZrZ), with lithium disilicate crowns (ZrL), or with PEEK crowns (ZrP). The specimens were artificially aged in a chewing simulator for 1.2 million cycles of dynamic loading with simultaneous thermal cycling and then loaded to fracture in the universal testing machine. Shapiro-Wilk test was used to test for normality. Oneway analysis of variance followed by post hoc analysis using Bonferroni test was used to detect statistically significant differences among groups. Results: All specimens survived the artificial aging process simulating 5 years of clinical service. The fracture patterns and means of the fracture strength (N) varied between groups: TiZ = 4,926 N; TiL = 3,706 N; TiP = 3,878 N; ZrZ = 5,529 N; ZrL = 2,826 N; and ZrP = 3,967 N. Conclusion: Although the tested combinations showed different fracture patterns and loads, all tested abutment and crown materials and their different combinations could be considered to have fracture strengths suitable for clinical application.