Artificial intelligence (AI) models have been developed for different applications, including the automatic design of occlusal devices; however, the design discrepancies of an experienced dental laboratory technician and these AI automatic programs remain unknown. The purpose of this in vitro study was to compare the overall, intaglio, and occlusal surface discrepancies of the occlusal device designs completed by an experienced dental laboratory technician and two AI automatic design programs. Virtually articulated maxillary and mandibular diagnostic casts were obtained in a standard tessellation language (STL) file format. Three groups were created depending on the operator or program used to design the occlusal devices: an experienced dental laboratory technician (control group) and two AI programs, namely Medit Splints from Medit (Medit group) and Automate from 3Shape A/S (3Shape group) (n=10). To minimize the discrepancies in the parameter designs among the groups tested, the same printing material and design parameters were selected. In the control group, the dental laboratory technician imported the articulated scans into a dental design program (DentalCAD) and designed a maxillary occlusal device. The occlusal device designs were exported in STL format. In the Medit and 3Shape groups, the diagnostic casts were imported into the respective AI programs. The AI programs automatically designed the occlusal device without any further operator intervention. The occlusal device designs were exported in STL format. Among the 10 occlusal designs of the control group, a random design (shuffle deck of cards) was used as a reference file to calculate the overall, intaglio, and occlusal discrepancies in the specimens of the AI groups by using a program (Medit Design). The root mean square (RMS) error was calculated. Kruskal-Wallis, and post hoc Dwass-Steel-Critchlow-Fligner pairwise comparison tests were used to analyze the trueness of the data. The Levene test was used to assess the precision data (α=.05). Significant overall (P<.001), intaglio (P<.001), and occlusal RMS median value (P<.001) discrepancies were found among the groups. Significant overall RMS median discrepancies were observed between the control and the Medit groups (P<.001) and the control and 3Shape groups (P<.001). Additionally, significant intaglio RMS median discrepancies were found between the control and the Medit groups (P<.001), the Medit and 3Shape groups (P<.001), and the control and 3Shape groups (P=.008). Lastly, significant occlusal RMS median discrepancies were found between the control and the 3Shape groups (P<.001) and the Medit and 3Shape groups (P<.001). The AI-based software programs tested were able to automatically design occlusal devices with less than a 100-µm trueness discrepancy compared with the dental laboratory technician. The Levene test revealed significant overall (P<.001), intaglio (P<.001), and occlusal (P<.001) precision among the groups tested. The use of a dental laboratory technique influenced the overall, intaglio, and occlusal trueness of the occlusal device designs obtained. No differences were observed in the precision of occlusal device designs acquired among the groups tested.