Aim: This study was designed to compare the retention strength of monolithic CAD/CAM PEEK crowns to that of CAD/CAM monolithic YTZP-zirconia crowns, both resin-cemented to epoxy resin dies resembling lower molar teeth; after thermomechanical aging simulating 3 months of in-vivo service. Materials and methods: 22 identical epoxy dies, resembling the preparation of a lower second molar (4mm height, 6° axial convergence and 1 mm-thick deep chamfer finish line), were produced by replicating one master stainless steel die via 22 polyvinyl siloxane impressions. The epoxy dies were randomly equally distributed into 2 groups (Zr and P groups); 11 dies each. The first (control) group (Zr) received CAD/CAM milled monolithic Y-TZP zirconia crowns (Katana™ ML), while the other group (intervention) received CAD/CAM milled monolithic PEEK crowns (breCAM.BioHPP™). Two opposing, laterally projecting (mesial and distal) arms were included in the design of all crowns for the retention test. The fitting surfaces of crowns of both groups were sandblasted with 110-µm alumina particles. All crowns were cemented over their corresponding epoxy dies using the (hand-mixed) dual-cured, self-adhesive resin cement (RelyX™ U200) (3-kg seating force). Samples were stored in water incubator for 24 hours (37 °C); then, subjected to mechanical aging (37,500 cycles, 49 N load) with simultaneous thermocycling (300 cycles, 5-55 °C, 12 s dwell time). Retention strength was evaluated by vertically pulling-up the crowns from their corresponding dies, through the pull-out test performed via a universal testing machine (UTM). Failure modes were then observed under digital microscope. The mean dislodgment force (retention strength) for each group was calculated, and statistically compared using Student t-test. Statistical analysis was performed with three-way ANOVA. Pair-wise comparison of groups was made with the Tukey test. Pearson's Chi-Square test was used to analyze the failure modes. Results: PEEK crowns group (P) demonstrated statistically insignificant higher retention strength (171.28 N ± 26.30) than zirconia (Zr) crowns group (150.40 N ± 24.40). “Mixed" failure mode was predominant in both groups, followed by the adhesive “cement on crown" failure-mode.