This study tested the hypotheses that (1) cervical total disc replacement with a compressible, six-degree-of-freedom prosthesis would allow restoration of physiologic range and quality of motion, and (2) the kinematic response would not be adversely affected by variability in prosthesis position in the sagittal plane. Twelve human cadaveric cervical spines were tested. Prostheses were implanted at C5-C6. Range of motion (ROM) was measured in flexion-extension, lateral bending, and axial rotation under ± 1.5 Nm moments. Motion coupling between axial rotation and lateral bending was calculated. Stiffness in the high flexibility zone was evaluated in all three testing modes, while the center of rotation (COR) was calculated using digital video fluoroscopic images in flexion-extension. Implantation in the middle position increased ROM in flexion-extension from 13.5 ± 2.3 to 15.7 ± 3.0° (p < 0.05), decreased axial rotation from 9.9 ± 1.7 to 8.3 ± 1.6° (p < 0.05), and decreased lateral bending from 8.0 ± 2.1 to 4.5 ± 1.1° (p < 0.05). Coupled lateral bending decreased from 0.62 ± 0.16 to 0.39 ± 0.15° for each degree of axial rotation (p < 0.05). Flexion-extension stiffness of the reconstructed segment with the prosthesis in the middle position did not deviate significantly from intact controls, whereas the lateral bending and axial rotation stiffness values were significantly larger than intact. Implanting the prosthesis in the posterior position as compared to the middle position did not significantly affect the ROM, motion coupling, or stiffness of the reconstructed segment; however, the COR location better approximated intact controls with the prosthesis midline located within ± 1 mm of the disc-space midline. Overall, the kinematic response after reconstruction with the compressible, six-degree-of-freedom prosthesis within ± 1 mm of the disc-space midline approximated the intact response in flexion-extension. Clinical studies are needed to understand and interpret the effects of limited restoration of lateral bending and axial rotation motions and motion coupling on clinical outcome.