Background: Postoperative pain following laparoscopic cholecystectomy remains clinically relevant despite the minimally invasive nature of the procedure. Peripheral nerve blocks are integral to multimodal analgesia strategies, with the subcostal transversus abdominis plane (TAP) block widely used for somatic pain control. The anterior subcostal quadratus lumborum (QL) block has been proposed to provide broader analgesia, including visceral pain modulation, potentially improving early recovery. Objective: This study aimed to compare the perioperative analgesic efficacy of the anterior subcostal quadratus lumborum block and the subcostal transversus abdominis plane block in patients undergoing laparoscopic cholecystectomy. Methods: In this prospective, single-blind, randomized controlled trial, 48 adult patients undergoing elective laparoscopic cholecystectomy under general anesthesia were randomized to receive either an anterior subcostal QL block or a subcostal TAP block after anesthesia induction. Standardized anesthetic and postoperative analgesic protocols were applied. The primary outcome was postoperative pain intensity assessed using the Numerical Rating Scale (NRS) at 1, 6, 12, and 24 h postoperatively and categorized as mild (NRS 1–3), moderate (NRS 4–6), or severe (NRS 7–10). Secondary outcomes included intraoperative fentanyl consumption, intraoperative nociceptive index (qNox), intraoperative mean arterial pressure (MAP), total morphine consumption and time to first morphine administration within 24 h postoperatively, Quality of Recovery-15 (QoR-15) score at 24 h, pain characteristics, and block-related adverse events. Results: Patients in the QL block group experienced a significantly higher proportion of mild pain at 1 hour (p = 0.023) and 6 h (p = 0.033) postoperatively compared with the TAP block group. No significant differences were observed at 12 h, and all patients in both groups reported mild pain at 24 h. Intraoperative fentanyl requirements, intraoperative qNox values, total postoperative morphine consumption, and time to first morphine administration were comparable between groups. Mean arterial pressure during pneumoperitoneum insufflation was significantly lower in the QL group (p = 0.024). Although mean QoR-15 scores did not differ significantly, categorical analysis demonstrated a more favorable recovery profile in the QL group (p = 0.046). Adverse events were infrequent and mild, with no cases of local anesthetic systemic toxicity. Conclusion: The anterior subcostal quadratus lumborum block provides superior early postoperative analgesia and improved recovery quality distribution compared with the subcostal transversus abdominis plane block, while maintaining comparable opioid requirements and safety. This technique represents a valuable component of multimodal analgesia and enhanced recovery pathways for laparoscopic cholecystectomy. © 2026