Background: Craniosynostosis is a congenital condition characterized by the premature fusion of cranial sutures, leading to potential complications such as abnormal skull growth, increased intracranial pressure, and cognitive delays. Traditionally, open cranial vault reconstruction (OCVR) has been used to treat this condition. However, it is highly subjective and greatly dependent on the surgeon's expertise, which can lead to residual deformities and the need for reoperation. Effective preoperative planning can greatly improve surgical outcomes, although the major challenge is accurately translating this plan into the clinical setting. Recently, augmented reality (AR) and 3D printing have emerged as promising technologies to facilitate this endeavor. In this work, we propose three alternatives, leveraging these technologies, to guide the precise repositioning of remodeled bone fragments in the patient. Methods: The three guidance methods are AR on a tablet, AR with Microsoft HoloLens 2, and 3D-printed spacers. The accuracy of each method was assessed by measuring the deviation of each bone fragment from the virtual surgical plan (VSP) in a simulated environment using 3D-printed phantoms based on a 14-month-old boy with trigonocephaly. The same assessment was also performed during his actual surgery. Results: All three guidance methods demonstrated similar levels of accuracy, with mean placement errors below 1 mm in all cases. The AR systems allowed for real-time adjustments, enhancing precision. Statistical analysis showed no significant differences in error rates between the different methods or attempts. Conclusions: Integrating AR and 3D printing into craniosynostosis surgery holds great potential for improving OCVR. While 3D-printed spacers are useful when digital technologies are unavailable, AR-based methods provide more comprehensive guidance. Nevertheless, our study suggests that the choice may depend more on the specific clinical context, user-specific skills, and available resources rather than on a clear superiority of one method over the others. The files presented in this repository contain the supplementary data that complements the article: Alicia Pose-Díez-de-la-Lastra, Mónica García-Sevilla, Austin Tapp, Manuel Tousidonis, Juan-Vicente Darriba-Alles, Marius George Linguraru, Javier Pascau, Santiago Ochandiano. Microsoft HoloLens 2 vs. Tablet-based Augmented Reality and 3D printing for fronto-orbital reconstruction of craniosynostosis: A case study. 3D Printing in Medicine. 2025. Should you have any questions, please, do not hesitate to contact us at apose@ing.uc3m.es.