The aim of this study was to compare the reliability of both linear and angular measurements conducted on two-dimensional (2D) lateral cephalometric images and three-dimensional (3D) cone-beam computed tomography-generated cephalograms derived from various rendering software. Pre-treatment cephalometric digital radiographs of 15 patients and their corresponding cone beam computed tomographic images were randomly selected. Vista Dent OC as 2D, In vivo 5.1.2, Maxilim and Romexis software were used to generate cephalograms from the CBCT scans (NewTom 3G, QR Verona, Italy). In total, 19 cephalometric landmarks were identified and 18 widely used (11 linear, 7 angular) measurements were performed by an independent observer. MannÀWhitney and KruskallÀWallis H tests were also used to compare the four methods (p < 0.05). Intra-class correlation coefficients (ICCs) were used to examine the intra-observer reliability. Intra-observer examinations showed various unreliable ICCs, which was an indication of poor reproducibility for condylion-gnathion (Co-Gn), gonion-mentum (Go-Me), anterior nasal spinamentum (ANS-Me), Wits for all 2D and 3D rendering software (p > 0.05). The ICCs for Vista Dent OC (2D) measurements indicated high reproducibility (p < 0.05). The 2D and 3D generated cephalograms from various rendering software were found to be similar; however, measurements on curved surfaces are not easily reproducible for 3D software.