INTRODUCTION: Craniofacial scoliosis secondary to unicoronal synostosis (UCS) has been widely observed to encompass the vault, the cranial base, and the face. While the basic differences have been recorded, a thorough analysis of the cranial base and intra-cranial craniometric, and volumetric differences have not. We hypothesized that patients with UCS have deviation of the vault, cranial base, and face resulting in significant differences in skull base morphology and segmental cranial vault volume relative to non-affected controls. METHODS: UCS patients with high-resolution pre-operative CT scans were collected from our IRB-approved, prospective, craniofacial registry. Patients with UCS were compared to a trauma registry (without cranial pathology) and positive controls (positional plagiocephaly). Mimics® software was used to compare those with UCS to controls for a series of standardized craniometric angles and distances. A segmented volumetric analysis of anterior, middle, and posterior cranial fossae was performed, as well. RESULTS: The study included 18 patients with UCS and 19 controls. The average age at time of scan was 5.7 ± 2.2 months for UCS and 5.7 ± 2.9 months for controls (p=0.988). Overall cranial vault volume did not differ between UCS and controls (p= 0.250). Nearly all angles measured between the synostosed side of UCS and control patients—posterior fossa deflection angle (18.0 ± 5.2 vs. 2.4 ± 2.1, respectively), petrous ridge angle (104.0 ± 5.7 vs. 126.6 ± 4.9, respectively), external acoustic meatus angle (92.3 ± 4.8 vs. 100.3 ± 3.4, respectively), articular fossa angle (82.5 ± 3.8 vs. 89.9 ± 4.0, respectively), and bifrontal angle (152.2 ± 6.9 vs. 143.7 ± 8.3, respectively)—were significantly different (p<0.002). Three volumetric ratios comparing the synostosed side to the contralateral were significantly less than controls: anterior (0.44 ± 0.03 vs. 0.5 ± 0.01, p<0.001), middle (0.45 ± 0.02 vs. 0.5 ± 0.02, p<0.001), and posterior (0.46 ± 0.02 vs. 0.50 ± 0.02, p<0.001). The ratio of total middle volume to total cranial volume was larger in UCS patients vs. controls, but the posterior ratio was smaller: anterior (0.13 ± 0.02 vs. 0.12 ± 0.02, p=0.545), middle (0.50 ± 0.05 vs. 0.42 ± 0.04, p=0.001), and posterior (0.37 ± 0.05 vs. 0.45 ± 0.03, p=0.001). CONCLUSION: This study provides quantitative evidence of the degree of angulation and torsion of the cranial base in UCS and its profound effect on volumetric differences in the cranial vault, with significant restriction on the synostosed side and compensatory expansion on the non-synostosed side. Future work will focus on the effects of volumetric differences on cerebral architecture and postoperative volumetric changes.