The primary objective of this work was to investigate the effect of material selection and tooth position on orthodontic aligner biomechanics. Additionally, material property changes with thermoforming were studied to elucidate its role in material performance in-vitro. An orthodontic simulator (OSIM) was used to evaluate forces and moments at 0.20 mm of lingual displacement for central incisor, canine and second premolar using Polyethylene terephthalate (PET), Polyurethane (PU) and Glycol-modified polyethylene terephthalate (PET-G) materials. The OSIM was scanned to generate a model used to fabricate aligners using manufacturerspecified thermoforming procedures. Repeated measures of MANOVA was used to analyze the effect of teeth and material on forces/moments. The role of thermoforming was evaluated by flexural modulus estimated by 3-point bend tests. -Pre-thermoformed and post-thermoformed samples were prepared using as-received sheets and those thermoformed over a simplified arch using rectangular geometry, respectively. Groups were compared using Two-way ANOVA. The PET, PU, and PET-G materials exerted maximum buccal force and corresponding moments on the canine. PU exerted more buccal force than PET-G on the canine and second premolar, and more than PET on the second premolar. The impact of thermoforming varied according to the specific polymer: PET-G remained stable, there was a slight change for PET, and a significant increase was noted for PU from pre-thermoformed to post-thermoforming. The results of this study elucidate the influence of material and arch position on the exerted forces and moments. Further, the mechanical properties of thermoplastic materials should be evaluated after thermoforming to characterize their properties for clinical application.