ObjectiveTo evaluate the screw-placement accuracy and technical advantages of patient-specific three-dimensional (3D)-printed drill guide-assisted C2 pedicle screw placement in bone models derived from patients with basilar invagination, and to provide evidence for clinical screw-placement strategies in high-risk craniocervical junction deformities. MethodsPreoperative thin-slice CT data from 9 patients with basilar invagination treated between June 2016 and July 2025 were used. For each patient, two 1∶1-scale 3D-printed upper cervical spine models were fabricated, and assigned to the guide-assisted group and the freehand group by computer-generated block randomization. Bilateral C2 screws were inserted by the same spine surgeon according to a standardized protocol. In the guide-assisted group, screw placement was performed in the following sequence: guide positioning, guide pin insertion, guide removal followed by enlargement drilling, tapping, and screw insertion. In the freehand group, screw placement was performed by anatomical landmark-based localization, stepwise drilling with fluoroscopic correction, enlargement drilling and tapping, and screw insertion. The primary outcomes were postoperative CT-based Gertzbein-Robbins (GR) grading of screw position and the GR grade 0/1 acceptability rate. Secondary outcomes included entry-point deviation, axial angle deviation, and the number of fluoroscopic exposures. ResultsThe two assessors showed good agreement in GR grading, with a Kappa coefficient>0.80, indicating reliable evaluations. Postoperative CT assessment showed that the overall distribution of GR grades was significantly better in the guide-assisted group than in the freehand group (P<0.05). The GR grade 0/1 acceptability rate was higher in the guide-assisted group, but the difference was not significant (P>0.05). Entry-point deviation, axial angle deviation, and the number of fluoroscopic exposures were all significantly lower in the guide-assisted group than in the freehand group (P<0.05). ConclusionPatient-specific 3D-printed drill guides can reduce geometric deviations in C2 pedicle screw placement in basilar invagination and decrease the number of fluoroscopic exposures. They show a potential advantage in improving the GR grade 0/1 acceptability rate; however, further clinical studies with larger samples are needed for verification.