Purpose <p>The aim of the present study is to analyze the feasibility of a new optimized C1 lateral mass and C2 pedicle screw method that has a suitable trajectory for a range of anatomical variations to decrease the risk of vertebral artery injury.</p> Methods <p>The craniovertebral junction of 17 cadavers (34 sides) were dissected after performing thin-cut computed tomography. The screw entry points, targets, angles, and lengths of the trajectories were performed for C1 lateral mass and C2 pedicle. We particularly focused on the morphometric features and the safety of trajectories in cadavers with vascular and bony variations.</p> Results <p>For the C1 lateral mass, the ideal medial and cranial angles were 13.4° ± 1.0° and 14.7° ± 1.1°, respectively. For the C2 pedicle screw, the cranial and medial angles were 27.7° ± 1.4° and 20.4° ± 1.5°, respectively. High-riding vertebral arteries (HRVA) were observed in 35.3% of all cadavers. The incidence of an arcuate foramen was 47% among all sides and its coexistence with an HRVA among all cadavers was 23.5%.</p> Conclusion <p>Preoperative pedicle-oriented radiological evaluation is crucial before C1 lateral mass and C2 pedicle screw placement because of the high incidence of bony and vascular variations. Using our safe C2 pedicle trajectory, a longer and safer screw course that preserves the vertebral artery can be achieved with a more feasible cranial angle, even with HRVAs, with the exception of narrow pedicle anatomy.</p>