Mechanical testing machines are used to evaluate kinematics, kinetics, wear, and efficacy of spinal implants. The simulation of "physiological" spinal loading conditions necessitates the simultaneous use of multiple actuators. The challenge in achieving a desired loading profile lies in achieving close synchronization of these actuators. Errors in load application can be attributed to both the control system and the intrinsic sample response. Moreover, the presence of friction in the setup can have an impact on the measured outcome. The optimization of setup parameters can substantially improve the ability to simulate spinal loading conditions and obtain reliable data on implant performance. In this study, a reproducible kinematic test protocol was developed to evaluate the sensitivity of the kinetic response (i.e., measured loads, moments, and stiffnesses) of a cervical disc prosthesis to several testing parameters. In this context, five ceramic ball and socket sample implants were mounted in a 6 DOF material testing machine and tested with a constant axial compressive force of 100 N in two motion modes: 1) flexion-extension (±7.5°) and 2) lateral bending (±6°). Parameters including rotation rate, slider friction, friction between the samples' articulating surfaces, and moment arm were considered to determine their effects on measured kinetic parameters. The sensitivity analysis indicated that all setup parameters except friction between the samples' articulating surfaces had a substantial effect on the results. The findings were then compared to predictions from a free body diagram to determine the optimal setup parameters. Consequently, the setup with the lowest rotation rate and employing passive sliders yielded results that were consistent with the free body diagram. This study demonstrated the significance of a comprehensive setup evaluation for reliable and reproducible testing of spinal implants, also for comparison between labs.