BACKGROUND: Robot-assisted transaxillary thyroidectomy (RATT) involves extensive flap dissection, leading to significant postoperative pain. This study evaluated the efficacy of pectoral nerve II (PECS II) block in pain relief, opioid reduction, and recovery enhancement. METHODS: This prospective, randomized controlled trial included 83 patients undergoing elective RATT for thyroid conditions. Patients were assigned to the block group (n = 42) or non-block group (n = 41). Pain was assessed using the visual analog scale (VAS) at 1, 4, 24, and 48 hours postoperatively. Secondary outcomes included opioid consumption and Quality of Recovery-15 (QoR-15K) scores at discharge. RESULTS: The PECS II block group had significantly lower VAS scores at 1 h (3.6 ± 2.5 vs. 6.3 ± 2.3, P <
0.001), 4 h (2.6 ± 2.1 vs. 4.3 ± 2.5, P = 0.002), and 24 h (2.0 ± 1.6 vs. 3.2 ± 2.0, P = 0.002). Opioid consumption was significantly lower in the block group (median: 1 [0.75, 3] vs. 3 [2, 3.5], P = 0.001). QoR-15K pain subdimension scores were higher in the block group (14.5 [12, 17] vs. 10 [8, 14], P <
0.001), while other recovery aspects were comparable. CONCLUSIONS: The PECS II block significantly reduces pain and opioid use in RATT patients, enhancing recovery quality. This opioid-sparing approach supports multimodal pain management, ensuring safer and more comfortable postoperative recovery.