ABSTRACT Objective: The purpose of this study was to evaluate the impact of a treatment with electro-neuro-feedback (ENF), a portable transcutaneous electrical nerve stimulation (TENS) device, on the clinical outcome and inflammatory biochemical parameters related to the impacted lower third molar surgery. Materials and Methods: A randomized, split-mouth, and single-blind study was conducted on 32 patients requiring lower third molars extractions and referred to the Oral Surgery Unit of the School of Dentistry of the University of Messina. Every patient underwent surgical removal of both lower third molars. The first extraction included a placebo (electrodes placement with turned-off device) treatment following the surgery, while the second had the ENF used next to the avulsion and the following days. Clinical parameters were collected 4 days before, immediately after, 2, 4, and 7 days after the surgical procedure. Biochemical parameters were obtained 1 day before the surgical removal and 7 days after. Data were processed using Wilcoxon–Mann–Whitney test, with significance being set at P < 0.05. Results: Clinical outcome parameters showed a significant improvement after the ENF treatment, while considered inflammatory markers expressed different patterns. Conclusions: ENF, a reliable portable TENS device, has demonstrated to be a useful tool in the managing of the postsurgical phases, reducing edema, pain, and consequent pain-killers consumption.