Background <p>Advances in minimally invasive techniques, enhanced recovery protocols, and regional pain management have improved postoperative outcomes. However, visceral pain and postoperative nausea and vomiting (PONV) continue to be challenging after minimally invasive procedures. Intraoperative autonomic neural blockade (ANB), which interrupts the afferent nerves transmitting these impulses, has effectively addressed these challenges, as demonstrated in previous publications. This randomized trial evaluates its efficacy in laparoscopic cholecystectomy.</p> Methods <p>In this double-blind, randomized controlled trial, 62 patients undergoing elective laparoscopic cholecystectomy were assigned to receive ANB with Bupivacaine and Dexamethasone (intervention group) or no blockade (control group). All patients received standard TAP, subcostal blocks, low-pressure pneumoperitoneum, and ERAS-based care. The primary outcome was Acetaminophen consumption. Rescue analgesic use was assessed at 1, 24, and 48&#xa0;h postoperatively. Secondary outcomes included pain scores at 1, 24, and 48&#xa0;h and the incidence of nausea and vomiting.</p> Results <p>Baseline characteristics were similar between groups. Pain scores were significantly lower in the ANB group at 1, 24, and 48 h (0.42 vs. 2.52 at 1h; <i>p</i> &lt; 0.0001). Acetaminophen consumption was markedly reduced over 48 h (0.42 vs. 2.33 doses; <i>p</i> &lt; 0.0001). Fewer patients required NSAIDs or Codeine rescue analgesia, and nausea/vomiting was less frequent in the ANB group. No adverse events were reported.</p> Conclusions <p>This study demonstrates that ANB significantly reduces the analgesic requirements and autonomic symptoms after laparoscopic cholecystectomy, even when added to comprehensive multimodal care. These findings support its broader use in minimally invasive surgery (MIS), where autonomic afferent input predominates by targeting the appropriate pathways.</p> Graphical abstract <p></p>