Abstract Background Recently, several case reports and limited randomized studies have shown that quadratus lumborum blocks (QLB) are effective in providing pain relief after intra-abdominal and retroperitoneal operations. Additionally, robot-assisted partial nephrectomy (RAPN) has been proposed as a promising operative treatment for renal carcinoma because it enables early recovery and ambulation. Therefore, we aimed to evaluate the analgesic and opioid-sparing effects of a single-injection QLB in patients undergoing RAPN to determine its role in an early recovery program. Methods Fifty-six patients undergoing elective RAPN under general anesthesia were randomized to two equally sized groups. Patients were randomly allocated to receive either a unilateral QLB (n = 28) with 0.375% bupivacaine 0.5 mL/kg (QLB group) or a conventional scheme (n = 28) (control group). The QLB technique, termed QLB2, was performed as first described by Blanco. The primary outcome was visual analog scale (VAS) scores with movement at 6 h postoperatively. The secondary endpoints were morphine consumption at different time periods after surgery, morphine-related side effects, and assessment of postoperative rehabilitation. Results Both the VAS pain scores and cumulative opioid consumption were significantly lower in the QLB group at 6 h after surgery as compared with results in the control group (all P