This study proposed a pedicle screw design where the proximal 1/3 of the screw is unthreaded to improve fixation in posterior spinal surgery. This design was also expected to reduce the incidence of mechanical failure often observed when an unsupported screw length is exposed outside the vertebra in deformed or degenerated segments. The aim of this study was to evaluate the fatigue life of the novel pedicle screw design using finite element analysis and mechanical testing in a synthetic spinal construct in accordance with American Society for Testing and Materials (ASTM) F1717. The following setups were evaluated: (i) pedicle screw fully inserted into the test block (EXP-FT-01 and EXP-PU-01; full thread (FT), proximal unthread (PU)) and (ii) pedicle screw inserted but leaving an exposed shaft length of 7.6 mm (EXP-FT-02 and EXP-PU-02). Corresponding finite element models FEM-FT-01, FEM-FT-02, FEM-PU-01, and FEM-PU-02 were also constructed and subjected to the same loading conditions as the experimental groups. The results showed that under a 220 N axial load, the EXP-PU-01 group survived the full 5 million cycles, the EXP-PU-02 group failed at 4.4 million cycles on average, and both EXP-FT-01 and EXP-FT-02 groups failed after less than 1.0 million cycles on average, while the fatigue strength of the EXP-FT-02 group was the lowest at 170 N. The EXP-FT-01 and EXP-FT-02 constructs failed through fracture of the pedicle screw, but a rod fractured in the EXP-PU-02 group. In comparison to the FEM-FT-01 model, the maximum von Mises stress on the pedicle screw in the FEM-PU-01 and FEM-PU-02 models decreased by −43% and −27%, respectively. In conclusion, this study showed that having the proximal 1/3 of the pedicle screw unthreaded can reduce the risk of screw fatigue failure when used in deformed or degenerated segments.