Background: Clear aligners (CA) are used 22 h daily, creating a bite-block effect. This work aims to (i) analyze occlusal changes before the beginning of treatment, after the first set of CA and after the use of additional aligners; (ii) compare planned occlusal contacts with the ones obtained after the first set of CA; (iii) analyze the occlusal changes occurred after reaching the orthodontic goals after 3 months of using CA only at night; (iv) evaluate and characterize which tooth movements did not allow the treatment to be completed at the end of the first set of aligners, and finally (v) verify the possible relation between the changes in occlusal contact and areas and parameters such as case complexity and facial biotype. Materials and Methods: A quantitative, comparative, and observational longitudinal cohort study design was implemented to evaluate the clinical data and the complexity levels of cases receiving CA. A non-probabilistic and convenience sample of 82 individuals was recruited. The orthodontic malocclusion traits were classified as simple, moderate, or complex corrections based on the basis of the Align®recommendations with the Invisalign®evaluation tool. According to the Invisalign®criteria, patients need only one complex problem for their case to be classified as complex. Meshlab®v. 2022.02, ClinCheck®version Pro 6.0, My-Itero®version 2.7.9.601 5d plus, and IBM®SPSS Statistics software (Statistical Program for Social Sciences), version 27.0 for Windows were the software®used. Results: A statistically significant decrease in area and occlusal contacts number were observed from before the start of orthodontic treatment (T0) to the end of treatment (T1). The changes in the occlusal area (from T0 to T1) were statistically different between hyperdivergent (28.24 [15.51–40.91]) and hypodivergent (16.23 [8.11–24.97]) biotypes (p= 0.031). A significant difference between the hyperdivergent (4.0 [2.0–5.0]) and normodivergent (5.5 [4.0–8.0]) group was found in T1 for the anterior contacts (p= 0.044). Anterior contacts obtained were significantly higher than the planned (p= 0.037) Between T1 and T2 statistically significant increases of occlusal areas, posterior and total contacts were observed. Conclusions: Occlusal contact and area were decreased, either at the end of the first set or after the use of additional aligners. Anterior occlusal contacts obtained were higher than planned as opposed to posterior occlusal contacts obtained. The hardest tooth movements to achieve to complete the treatment were distalization, rotation, and posterior extrusion. After completing orthodontic treatment (T1) to 3 months after (T2) using additional aligners only at night, posterior occlusal contacts were significantly increased, which could be due to the natural settling of the teeth in this period.