BACKGROUND: Pain is an important issue in botulinum toxin injection. Vibration anesthesia is a noninvasive method for pain alleviation, but few studies have reported its use during botulinum toxin injection. OBJECTIVES: The aim of this study was to investigate whether vibration anesthesia was effective and safe for pain reduction during botulinum toxin injection for masseter reduction. METHODS: A randomized split-face controlled trial was performed in patients who required masseter reduction. Vibration anesthesia was randomly administered on either side. Study outcomes were pain scores on a visual analog scale, duration of effect, satisfaction, and complications. Intergroup comparison and linear regression analyses were performed. RESULTS: In a total of 216 patients, the pain score on the vibration side (2.97 ± 1.44) was significantly lower than that on the nonvibration side (4.72 ± 2.13) (P <
.0001), with a higher proportion of mild pain. Linear regression showed that a history of injection and more injection points and doses increased the pain, whereas a 2-mL syringe reduced the pain compared to a 1-mL syringe. Side effects were found in 19 patients and 21 sides (7%), but were not associated with vibration. High satisfaction was reported. A cadaver experiment confirmed that vibration did not alter the diffusion radius and depth of injection. CONCLUSIONS: Vibration anesthesia significantly relieved pain during botulinum toxin injection for masseter reduction, and it did not cause adverse effects and or affect duration of effect. Therefore, we recommend vibration anesthesia, a larger syringe size, and fewer injection points to improve patient experience and satisfaction.