The surgical removal of mandibular third molars is frequently accompanied by significant postsurgicalsequelae, and different protocols have been described to decrease such adverse events. The aim of this study was to investigate the performance of piezosurgery compared with traditional rotating instrumentsduring mandibular third molar removal. A single-center, randomized, split-mouth study was performed using a consecutive series of unrelated healthy patients attending the Oral Surgery Unit of the University of Turin for surgical removal of bilateral mandibular third molar teeth. Each patient was treated, at the same appointment, using bur removal on 1 side of the mandible and a piezoelectric device on the contralateral side. The primaryoutcomes reported were postoperative pain, objective orofacial swelling, and surgical duration; secondary outcomes were gender, age, and possible adverse events. Analysis of variance or paired t test was used as appropriate to test any significant differences at baseline according to each treatment subgroup,and categorical variables were analyzed by χ(2) test. The study sample consisted of 100 otherwise healthy patients. The mean pain evaluation reportedby patients who underwent surgery with piezosurgery was significantly lower than that reported after bur (conventional) removal, reaching statistical difference after 4 days (P= .043). The clinical value oforofacial swelling at day 7, normalized to baseline, was lower in the piezosurgery group (P < .005). Theaverage surgical duration was significantly shorter in the bur group than in the piezosurgery group (P < .05). Three patients having bur removal developed short-term complications (2 dry sockets and 1temporaryparaesthesia), which totally resolved by 4 weeks. To date, this prospective investigation is the largest reported split-mouth study on piezosurgeryfor lower third molar tooth removal. This study also compared surgeons with different degreesof experience. It is evident that using a piezoelectric device can enhance the patient experience and decrease postoperative pain and swelling.