Background <p>The application of artificial intelligence (AI) to cephalometry has aroused growing interest due to its potential to optimize clinical workflows and improve efficiency. This study aimed to compare the differences and reproducibility of cephalometric measurements obtained using three methods: manual, WebCeph™ and AngelAligner™.</p> Methodology <p>30 patients were analysed, evaluating 9 measurements generated by the three methods at two different timepoints (T1 and T2).</p> Results <p>WebCeph™ presented significant differences as compared to the manual method in 7 of the 9 measurements (SNA, SNB, ANB, U1–APg, L1–APg, GoGn–SN, U1–L1), while AngelAligner™ displayed significant differences with the manual method in 4 measurements (SNA, U1–APg, L1–APg and U1–L1). Significant differences were found between the two AI-based systems in 7 of the 9 measurements. Reproducibility was high at all angles with the manual method, except for U1–L1, NLA, and LFH. The ICC was 1 for all measurements for both AI-based systems, indicating optimal reproducibility. When grouping by malocclusions, however, WebCeph™ presented greater differences with the manual method than AngelAligner™.</p> Conclusion <p>AI-based methods offered greater reproducibility than the manual method, but still require human supervision.</p>