Orthodontic treatment increasingly involves transparent aligners; however, biomechanical analysis of their treatment effects under clinical conditions is lacking. We compared the biomechanical efficacy and effectiveness of orthodontic treatment with transparent aligners and of fixed appliances in simulated clinical orthodontic treatment conditions using orthodontic finite element (FE) models. In the FE analysis, we used Model Activation/De-Activation analysis to validate our method. Fixed appliances and 0.75-mm and 0.5-mm thick transparent aligners were applied to a tooth-alveolar bone FE model with lingually-inclined and axially-rotated central incisors. Compared to the fixed appliance, the 0.75-mm and 0.5-mm transparent aligners induced 5%, 38%, and 28% and 21%, 62%, and 34% less movement of the central incisors and principal stress of the periodontal ligament and of the alveolar bone, respectively, for lingual inclination correction. For axial-rotation correction, these aligners induced 22%, 37%, and 40% and 28%, 67%, and 48% less tooth movement and principal stress of the periodontal ligament and of the alveolar bone, respectively. In conclusion, transparent aligners induced less tooth movement, it is sufficient for orthodontic treatment, but 0.5-mm aligners should be used for only mild corrections. Additionally, the Model Activation/De-Activation analysis method is suitable for FE analysis of orthodontic treatment reflecting clinical treatment conditions.