Percutaneous balloon compression (PBC) is a surgical intervention for Trigeminal neuralgia (TN). This study hypothesized PBC under regional anesthesia (RA) could reduce intraoperative hemodynamic fluctuations and postoperative adverse effects with equivalent efficacy compared to general anesthesia (GA).A retrospective cohort study with 159 patients who underwent PBC for TN at Xuanwu Hospital Capital Medical University between January 2022 and June 2023, with patients divided into RA (n = 60) and GA (n = 99) groups. Comparative analysis included intraoperative hemodynamics, postoperative efficacy and adverse reactions in 12 months follow-up.Compared to GA, RA resulted in more stable intraoperative hemodynamics and significantly reduced trigemino-cardiac reflex (TCR) risk (P < 0.01). And shorter operation duration, reduced medical expenses, and experienced lower extent and faster recovery of postoperative numbness, hypoesthesia and bite force decrease (P < 0.05). Additionally, the groups have similar pain scale decrease, oral analgesic reduction, patient satisfaction, and specific adverse events whin 1-year follow-up (P > 0.05).PBC under RA has similar efficacy to GA, without the need for general anesthesia management and resuscitation. RA had more stable intraoperative hemodynamics and lower TCR incidence, reduced perioperative risk, enabled intraoperative communication with conscious patients, allowing for real-time assessment and adjustment of balloon compression extent, so adverse events such as numbness were milder and recovered faster, shorter operation duration and medical expenses. It showed the clinical advantages and broad application prospects of PBC under regional anesthesia, benefiting more patients with TN in remote areas.Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.