BackgroundPiezocision is a minimally invasive surgical method aiming to accelerate tooth movement. However, its effect was found to be transient, appertaining to the regional acceleratory phenomenon (RAP). Hence, the aim of the study was to evaluate the effect of single and multiple piezocisions on the rate of orthodontic tooth movement (OTM). Moreover, the impact of both protocols on canine tipping and orthodontically induced inflammatory root resorption (OIIRR) has been assessed.MethodsThirty indicated patients for the therapeutic extraction of maxillary first premolars were enlisted in this split-mouth study, and they were randomly split into two equal groups, each including 15 subjects. In the Single Application Group (SAG), one side of the maxillary arch arbitrarily received a single piezocision before the onset of canine retraction, whereas in the Multiple Application Group (MAG), piezocisions were randomly performed on one side, three times on a monthly basis, over the 12-week study period. The contralateral sides of both groups served as the controls. Canine retraction was carried out bilaterally using nickel-titanium closed-coil springs, delivering 150 g of force, and the rate of tooth movement, as well as canine tipping were evaluated on a monthly basis, over a 3-month period. Cone-bean computed tomography scans were also conducted pre- and post- canine retraction, and OIIRR was assessed using Malmgren Index.ResultsThe reported outcomes revealed a significant increase in the amount of canine retraction, canine tipping, as well as root resorption scores on the experimental sides in both groups SAG and MAG post-retraction (p < 0.001). However, upon comparing the experimental sides in both groups, non-significant differences have been observed between them regarding all the assessed outcomes (p > 0.05).ConclusionsSingle and multiple piezocisions effectively accelerate OTM in comparison to conventional orthodontic treatment, with relative outcomes reported by both intervention frequencies. Accordingly, single piezocision is recommended as an adjunct to OTM. Furthermore, significant tooth tipping as well as a significantly higher root resorption risk accompanies both single and multiple piezocision applications in conjunction with OTM.Name of the RegistryClinicaltrials.govTrial Registration NumberNCT05782088Date of Registration23/03/2023 “Retrospectively registered”.URLhttps://clinicaltrials.gov/ct2/show/NCT05782088