Background: Quadratus lumborum block (QLB) is an effective analgesia that lowers opioid consumption after lower abdominal and hip surgeries. The subcostal approach to transmuscular QLB is a novel technique that can provide postoperative analgesia by blocking more dermatomes. The aim of this study is to evaluate the efficacy and viability of subcostal approach to QLB after laparoscopic nephrectomy. Methods: Sixty patients who underwent laparoscopic nephrectomy were randomly divided into the subcostal approach to QLB group (QLB group, n=30) and the control group (C group, n=30). All patients underwent ultrasound-guided subcostal approach to QLB in an ipsilateral parasagittal oblique plane at the L1–L2 level. The QLB group received 0.4 cc/kg of 0.3% ropivacaine, and the C group received 0.4 cc/kg of 0.9% saline. Postoperatively, a patient-controlled intravenous analgesic pump with sufentanil was attached to all the patients. The primary outcome was sufentanil consumption within the first 24 h after surgery. The secondary outcomes included the Ramsey sedation scale (RSS) scores and Bruggemann comfort scale (BCS) scores 6 h (T1), 12 h (T2), and 24 h (T3) after surgery, intraoperative remifentanil consumption, number of patients requiring rescue analgesia, time to recovery of intestinal function, mobilization time after surgery, and presence of side effects. Results: Sufentanil consumption within the first 24 h after surgery was significantly lower in the QLB group than in the C group (mean [standard deviation]: 34.1 [9.9] μg vs 42.1 [11.6] μg, P=.006). The RSS scores did not differ between the two groups, and the BCS scores of the QLB group at T1 and T2 time points was significantly higher than those of the C group(P＜0.05). The consumption of remifentanil intraoperatively and the number of patients requiring rescue analgesia were significantly lower in the QLB group (P＜0.05). Time to recovery of intestinal function and mobilization time after surgery were significantly earlier in the QLB group (P＜0.05). The incidence of postoperative nausea and vomiting was significantly lower in the QLB group (P＜0.05). Conclusions: The ultrasound-guided subcostal approach to QLB is an effective analgesic technique in patients undergoing laparoscopic nephrectomy as it reduces the consumption of sufentanil postoperatively.