<p>This study explores the feasibility and clinical value of using 3D-Slicer for preoperative planning in posterior C1–C2 fixation in patients with vertebral artery variations. A total of 118 patients who underwent posterior atlantoaxial fixation from January 2013 to December 2022 were included, with 51 cases utilizing 3D reconstruction and 67 cases not utilizing this approach. We employed four personalized screw placement strategies tailored to the type of vertebral artery variation: (1) Normal vertebral artery: pedicle screws for both C1 and C2; (2) Axis vertebral foramen variation: pedicle screws for C1 and Laminar screws for C2; (3) vertebral artery hypoplasia: pedicle screws for C1 and Laminar screws for C2; and (4) posterior atlas arch variation: lateral mass screws for C1 and pedicle screws for C2. The preoperative demographic and diagnostic data showed no significant differences between the groups. However, the use of 3D reconstruction with 3D-Slicer led to significantly improved outcomes, including 27.97% increase in optimal fixation method selection, reduced operating time, decreased intraoperative blood loss, and a lower risk of vertebral artery injury (VAI). The use of 3D-Slicer for preoperative planning in posterior C1-C2 fixation in patients with vertebral artery variations shows promising potential.</p>