Aim: An orthodontic treatment is described that combines the use of clear aligners and computer-guided piezocision to overcome the drawbacks of traditional corticotomy in accelerating orthodontic tooth movement. The relapse at the 2-year follow-up was also evaluated. Materials and methods: A 13-year-old male patient was selected and treated due to a molar Class II malocclusion with moderate dental crowding. Treatment time, oral health-related quality of life (OHRQoL), and periodontal indexes were assessed. To reduce the treatment time, computer-guided piezocision was utilized to perform flapless interproximal corticotomy cuts through the depth of the cortical bone. The orthodontic therapy using clear aligners began on the same day as the surgery. Results: The overall duration of the therapy was 6 months. There was an improvement in the periodontal indexes at the end of the therapy. An aggravation of OHRQoL only occurred for 3 days after surgery. The 2-year follow-up evaluation showed a relapse of 0.2 mm on the maxillary left lateral incisor and 0.25 mm on the mandibular right lateral incisor. Conclusion: The present case report describes the advantages of a combination of computer-guided piezocision and clear aligners to treat a Class II malocclusion with moderate crowding. Keywords: clear aligner appliance, CAD/CAM, accelerated tooth movement, orthodontics, piezocision, quality of life