(1) Background: To assess the clinical safety and efficacy of a new piezoelectric instrument for orthodontic clean-up; (2) Methods: An in-vitro comparative study on 75 teeth extracted for orthodontic reasons compared the tested method (Treatment 1) with two other procedures: One step finisher and polisher (Inverted cone One gloss Shofu Dental, Kyoto, Japan) (Treatment 2) and twelve-fluted tungsten carbide bur (123-603-00, Dentaurum, Pforzheim, Germany) and Sof-Lex discs Pop-On XT Kit (3M ESPE) (Treatment 3), with n:25 samples in each group. Clinical safety (enamel volume loss) and effectiveness (residual adhesive volume) were assessed using the structured light 3D scanner Atos Compact Scan (GOM GmbH) together with the support of Atos Professional software. The surfaces were scanned three times to assess: (i) the volume of the residual adhesive (RAV) after bracket removal; (ii) the volume of the relative residual adhesive (dAV) after the clean-up procedure; (iii) volume of the enamel loss (EVL); (3) Results: The mean RAV (mm3) was 0.239 ± 0.337; 0.069 ± 0.124, 0.120 ± 0.193 and the mean EVL (mm3) was 0.1870 ± 0.177, 0.187 ± 0.299 and 0.290 ± 0.205, for treatment 1, 2 and 3, respectively. The distribution was asymmetrical between groups in both cases; (4) Conclusions: The tested instrument proved to be effective and safe for post-orthodontic clean-up. With the increasing use of invisible aligners, the possibility of using an ergonomic and fast instrument is of benefit to both patient and practitioner.