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Statement of problem Intraoral scanners (IOSs), facial scanners (FSs), and computer-aided design (CAD) software programs have become powerful tools for treatment planning. However, discrepancies in perception regarding 2-dimensional (2D) or 3-dimensional (3D) simulations by dentists, dental students, and laypeople have not been analyzed. Purpose The purpose of this observational study was to analyze the perceptions of laypersons, dental students, and dentists regarding disparities of the maxillary dental midline and the occlusal plane when analyzing the dental discrepancies on 2D- and 3D-clinical simulations. Material and methods A female model was digitized by using an FS, IOS, and a full-face smile photograph. Dental discrepancies were simulated by using a 2D photograph (2D group) and 3D scan (3D group) of the model. In both simulation groups, 2 subgroups were produced. The occlusal plane of the first subgroup was modified in 1-degree increments without changing the dental midline or the position of the maxillary dental incisors. In the second subgroup, the occlusal plane was modified by using the same increments, but the maxillary central incisors and dental midline were altered to match the inclination of the occlusal plane. A total of 300 participants (N=300) were asked to rate the 2D images (N=12) and 3D videos (N=12) on a 1-to-6 scale and answer a questionnaire. Ordinal logistic regression was used to analyze the ratings. Results The ratings decreased with the increased tilt of the occlusal plane, and the layperson group gave consistently higher ratings than the other 2 groups. For dentists, the odds of giving a higher versus lower rating decreased by almost a half for each degree of tilt. However, for students, that effect was diminished by a positive interaction term, and for laypersons, the effect was even less. Students gave similar ratings to dentists, but laypersons gave higher ratings. As the age of the participants increased, however, the ratings also increased. The use of 3D versus 2D images had a positive effect on the ratings, but the effect decreased for the student observers and decreased even further for laypersons. Furthermore, midline alteration led to higher ratings but also resulted in worsening of the odds ratio for the tilt. Seventy percent of the dentists, 57% of the dental students, and 52% of the laypersons preferred 2D simulations to 3D simulations. Conclusions Dentists, dental students, and laypersons decreased their ratings with increased inclination of the occlusal plane; however, laypersons still graded all the 2D and 3D images as esthetically pleasant, giving consistently higher ratings than the dentists and dental students. Overall, 3D simulations obtained higher ratings than 2D images, but the positive effect decreased for the student observers and decreased even further for laypersons.