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PURPOSE.To verify the influence of computer-aided design/computer-aided manufacturing (CAD/CAM) implantsupported prostheses manufactured with cobalt-chromium (Co-Cr) and zirconia (Zr), and whether ceramic application, spark erosion, and simulation of masticatory cycles modify biomechanical parameters (marginal fit, screw-loosening torque, and strain) on the implant-supported system. MATERIALS AND METHODS. Ten full-arch fixed frameworks were manufactured by a CAD/CAM milling system with Co-Cr and Zr (n=5/group). The marginal fit between the abutment and frameworks was measured as stated by single-screw test. Screw-loosening torque evaluated screw stability, and strain analysis was explored on the implant-supported system. All analyses were performed at 3 distinct times: after framework manufacturing; after ceramic application in both materials' frameworks; and after the spark erosion in Co-Cr frameworks. Afterward, stability analysis was re-evaluated after 10 6 mechanical cycles (2 Hz/150-N) for both materials. Statistical analyses were performed by Kruskal-Wallis and Dunn tests (α=.05). RESULTS. No difference between the two materials was found for marginal fit, screwloosening torque, and strain after framework manufacturing (P>.05). Ceramic application did not affect the variables (P>.05). Spark erosion optimized marginal fit and strain medians for Co-Cr frameworks (P<.05). Screwloosening torque was significantly reduced by masticatory simulation (P<.05) regardless of the framework materials. CONCLUSION. Co-Cr and Zr frameworks presented similar biomechanical behavior. Ceramic application had no effect on the biomechanical behavior of either material. Spark erosion was an effective technique to improve Co-Cr biomechanical behavior on the implant-supported system. Screw-loosening torque was reduced for both materials after masticatory simulation.