Objective: The lack of adequate means to objectively characterize cranial shape contributes to ongoing controversies in the surgical management of craniosynostosis. Cranial shape analysis must address relevant clinical questions objectively and thoroughly and must be broadly applicable across the spectrum of normal and abnormal. Herein, we demonstrate and statistically validate an automated computed tomography (CT)-based application for 3-dimensional characterization of skull morphology. The technology is intended for application to diagnostic imaging, surgical planning, and outcomes assessment. Methods: Three-dimensional vector analysis (3DVA) was applied to craniofacial CT data, generating three-dimensional cranial surface point clouds. Validation: To assess accuracy, measurements derived from the 3DVA analysis of a CT scan of a skull phantom were compared to those made directly from the Digital Imaging and Communications in Medicine data on a Vitrea workstation. To assess reproducibility, 3 readers independently analyzed human head CT scans using 3DVA. Application: A normative database of 86 age-incremental pediatric patients was created. Preoperative craniosynostosis case datasets were analyzed using 3DVA and were compared with age-matched normative datasets. Results: Accuracy and reproducibility of less than 1% mean error and less than 0.5 mm standard error in all cases validated 3DVA-derived distances. Three-dimensional vector analysis point clouds provide qualitative and quantitative representations of morphology. Regional dysmorphology in craniosynostosis cases is demonstrated graphically. Conclusions: Three-dimensional vector analysis generated accurate, reproducible, and comprehensive craniofacial morphometric data. 3DVA may be used for paired data analysis (eg, a single subject undergoing surgical correction), comparative group data analysis, and craniofacial data archiving. The technique can provide objective characterization of craniofacial morphology previously not possible.