INTRODUCTION: Guided endodontics recently offers a conservative solution for conducting root canal treatment in cases of obliterated canals, but guide mispositioning remains a challenge. Recently, intraoral scanners (IOS) were proposed to detect deviations, but their effectiveness compared to expert visual assessments during guide insertion is uncertain. The objective of the present study was to primarily compare the risk of deviation predicted by an IOS versus expert assessment and secondarily identify factors influencing this risk. MATERIALS AND METHODS: Using a design of experiments approach, 16 endodontic guides were 3D-printed to assess the influence of guide thickness, internal offset, number of supporting teeth, and presence of windows. Guide positioning was evaluated digitally with the Trios 4 IOS to calculate angular deviation and visually by 10 experts using a Likert scale. The overall agreement between the value of angular deviation (less than or greater than 2°) and the expert score (positive or negative) was calculated. RESULTS: The mean angular deviation was 4.32° (SD=2.40°) and the mean expert score was -0.29 (SD=1.39). Angular deviation was most influenced by greater guide thickness (41.4%) and internal offset (27.0%), which both increased it. The most influential factor for expert scores was internal offset (90.5%), which decreased ratings. Agreement between IOS and expert scores averaged 60.6% (SD=39.1%), with the highest agreement for guides with a high internal offset. CONCLUSIONS: Experts effectively detected positioning errors with high internal offset but struggled with other factors, where IOS was more accurate. IOS shows promising potential for improving guide fitting in clinical practice.