The aim of this study was to generate 3D norms for a sample of adult subjects with normal accepted occlusion and balanced facial profile in centric relation (CR) using interocclusal mandibular splint and compare it to norms in simulated centric occlusion (CO).Materials and methods: A cross sectional observational study was performed on 37 Egyptian adult subjects ( 25 males and 12 females ) with an age range from 18-25 years havingbalanced facial proportions and Angle Class I skeletal, molar and canine relationship. All subjects had a full permanent dentition with the exception of the third molars. Arch length discrepancy ranged from 1 to 3 mm in each jaw within the three dimensions (vertical, anteroposterior and transverse), 2 to 3 mm overjet, 20-30% overbite and coincidental facial and dental midlines. Subjects with craniofacial deformities, pregnant female subjects, those who had been exposed to x-ray radiation within the last six months and those who had received previous orthodontic treatment were excluded from the study.First visit, impression taking was performed. Splint fabrication was done using 2 mm thickness hard vacuum sheets and the thickness was checked with the digital caliper to ensure 1-1.2 mm thickness of the sheet after fabrication.Thirty seven CBCT images were collected using the i-CAT CBCT machine. The subject`s head was oriented before imaging in the natural head position. The three-dimensional assessment was performed by In Vivo Dental Anatomage 5.3 software. The inter- and intra-observer reliability was confirmed after the 3D landmarks identification for randomly selected 10% of the sample by two observers, the researcher (observer1) and a colleague (observer2), and only for the researcher to do it twice with a gap of seven days between them.Nasion landmark (N point) was the point of origin where the three main reference planes (x, y, z) intersect. Reference planes were parallel to those of the machine representing the True spatial planes as found in previous studies82, 83. “3D Analysis” was based on thirty six cranial, maxillary and mandibular base landmarks located on each CBCT image, forty two angular and linear measurements between the different anatomical landmarks which were projected to the main reference system.Simulated CO were digitally done using In Vivo Dental Anatomage software version 5.3 “MD Studio” and “stitching” sections. “3D Analysis” were performed on the simulated COvolumes and difference in measurements between CR and CO measurements were tested statistically for significance.Results: The intra-observer, inter-observer reliability for landmarks showed high concordance with identical ICC and CCC.Means of different angular and linear measurements were collected from the three dimensional cephalometric norms in centric relation that can be used in orthodontics diagnosis and treatment planning.Regarding sex difference, linear measurements describing skeletal bases relationship the maxillary and mandibular lengths and effective lengths (A-JMid, Me-GoMid, CD-A and CD-Gn) and skeletal vertical measurements (AUFH, ALFH, ATFH, PTFH and PLFH) were found to be statistically significant higher in males than in females indicating larger male skulls..Results of showed that all measurements describing the maxilla and its relation to the cranium showed no statistically significant difference. In addition, all dental measurements were not influenced by the splint except the position of the lower incisor and the interincisal angle. However, a statistically significant difference (P ≤ 0.05) was found for all measurements describing the mandible, skeletal profile and skeletal vertical measurements (except AUFH).Conclusions:1. A three dimensional skeletal cephalometric analysis was established. Normative cephalometric data for adult Egyptians in centric relation was generated which can be used in orthodontic diagnosis and treatment planning.2. Linear skeletal measurements were higher in males than females indicating larger male skulls.3. The findings of this study indicated that the use of the splint did not affect the position of the maxilla and the dental measurements between CR and CO except for the position of the lower incisor and the interincisal angle. However, it did affect the skeletal profile and dentoskeletal mandibular measurements which could be of clinical significance.