© 2021 American Association of OrthodontistsIntroduction: The study aimed to evaluate and compare the effects of local platelet-rich fibrin (PRF) injection and piezocision applications on tooth movement during canine distalization, as well as to evaluate any changes in the periodontal parameters. Methods: Twenty-four patients were randomly divided into 2 groups. A randomly selected side of the maxillary arch received either PRF injection (PRF group) or piezocision (piezocision group). The contralateral sides of both groups served as the controls. After piezocision and PRF injection applications, canine distalization was initiated in both groups with a 150 g force. Patients were followed every 2 weeks for a total 12 of weeks. The following variables were evaluated: cephalometric measurements, the amount of canine distalization, molar mesialization, canine rotation, transversal changes in dental models, and periodontal parameters. Results: The amount of canine distal movement was found to be greater in the experimental sides than in the control sides in both groups at 12 weeks (P <0.05). There were no differences in the amount of molar mesialization, canine rotation, or transversal measurements in both groups when compared with the experimental sides with the control sides (P >0.05). There were no differences in the skeletal measurements or periodontal parameters in both groups (P >0.05). In both groups, the maxillary incisors were retroclined and retracted. Conclusions: PRF and piezocision accelerated tooth movement, but there were no differences between the 2 applications in terms of speed, amount, duration of tooth movement, or periodontal parameters during canine distalization.