Background: Robotic and hand-assisted laparoscopic nephrectomies are often associated with moderate to severe postoperative pain. The aim of the current study was to investigate the analgesic efficacy of the transmuscular quadratus lumborum (TQL) block for patients undergoing robotic or hand-assisted laparoscopic nephrectomy. Methods: Fifty patients were included in this single-center study. All patients were scheduled for elective hand-assisted or robotic laparoscopic nephrectomy under general anesthesia. Preoperatively, patients were randomly allocated to TQL block bilaterally with ropivacaine 60 mL 0.375% or 60 mL saline and all patients received standard multimodal analgesia and intravenous patient-controlled analgesia. Primary outcome was postoperative oral morphine equivalent (OME) consumption 0-12 hours. Secondary outcomes were postoperative OME consumption up to 24 hours, pain scores, time to first opioid, nausea/vomiting, time to first ambulation and hospital length of stay (LOS). Results: Mean (95% CI) OME consumption was significantly lower in the intervention group at 12 hours after surgery 50 (28.5 to 71.5) mg versus control 87.5 (62.7 to 112.3) mg, p=0.02. At 24 hours, 69.4 (43.2 to 95.5) mg versus 127 (96.7 to 158.6) mg, p<0.01. Time to first opioid was significantly prolonged in the intervention group median (IQR) 4.4 (2.8-17.6) hours compared with 0.3 (0.1-1.0) hours in the control group, p<0.001. No significant intergroup differences were recorded for time to first ambulation, pain scores, nausea/vomiting nor for LOS. Conclusion: Preoperative bilateral TQL block significantly reduced postoperative opioid consumption by 43% and significantly prolonged time to first opioid. Trial registration number: NCT03571490.