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Background Postoperative pain after laparoscopic colorectal surgery (LCS) is complex, involving both somatic and visceral components. Anterior subcostal quadratus lumborum block (QLB) is a novel regional technique that may provide dual analgesic coverage.Objective To evaluate the analgesic efficacy of ultrasound-guided anterior subcostal QLB in patients undergoing LCS.Design This prospective, randomized, observer-blinded trial included 60 adults scheduled for elective LCS at a university hospital between October 2024 and May 2025. Patients were randomly allocated to receive either bilateral anterior subcostal QLB or no regional anesthesia or local anesthetic infiltration (control).Main outcome measures The primary outcome was cumulative intravenous morphine milligram equivalent consumption at 24 hours postoperatively. Secondary outcomes included 12 hours intravenous morphine milligram equivalent consumption, pain scores (at rest and activity), time to first demand for patient-controlled analgesia (PCA), rescue analgesic/antiemetic use, block-related complications and recovery parameters.Results Data from 55 patients were analyzed (QLB (n=27); control (n=28)). The median 24-hour intravenous morphine milligram equivalent consumption was significantly lower in the QLB group than that in the control group (15 mg (Q1–Q3, 6.5–22 mg) vs 24.3 mg (Q1–Q3, 20.3–30.3 mg); p=0.006). Pain scores at all time points were significantly lower in the QLB group (p<0.001). Time to first PCA demand was prolonged (45 vs 20 min; p<0.001), and a smaller proportion of patients who underwent QLB required rescue analgesia (7.4% vs 92.8%) and antiemetics (18.5% vs 71.4%). No block-related complications were observed. QLB also shortened the median time to mobilization (12 vs 17 hours; p=0.026) and hospital stay (5 vs 6 days; p=0.008).Conclusions The anterior subcostal QLB was associated with reduced postoperative opioid use, lower pain scores and a lower incidence of postoperative nausea–vomiting after LCS, suggesting a potential role in enhancing recovery.Trial registration number NCT06653439; registration date: 20 October 2024.