Background and Objective: Erector spinae plane block (ESPB) has been reported to provide analgesia in open abdominal surgeries in case reports or case series. We aimed to compare the effectiveness of ESPB and anterior Quadratus Lumborum block (QLB III) as a postoperative analgesic for open nephrectomy. Methods: Seventy five patients scheduled for open nephrectomy were randomly allocated into three equal groups (25 each); group (C) patients operated under general anesthesia while in (QLB and ESPB) groups, patients received general anesthesia followed by unilateral (QLBIII or ESPB) respectively, with 0.3–0.4 ml/kg of bupivacaine 0.25%. The primary outcome was the 24 h cumulative morphine given postoperatively. The secondary outcomes were the first rescue analgesic time, postoperative pain score, time to perform technique and sensory block coverage. Results: The 24 cumulative morphine consumption and first rescue analgesic time were significantly higher and shorter, respectively, in control group compared to the QLB and ESPB groups with no significant difference between interventional groups. VAS score at rest and during movement was significant higher in control group at all different timing measurements compared to the interventional groups. The block performing time was significant shorter in ESPB compared to QLB and the coverage of QLB extends from T8 to L2 and ESPB from T6 to T12. Conclusion: The ESPB is as efficient as QLB III to provide analgesia and decrease perioperative opioid consumption, taking into account the technically challenging and the time consuming of QLB III making ESPB a highly promising alternative for postoperative pain relief following open nephrectomyBackground and Objective: Erector spinae plane block (ESPB) has been reported to provide analgesia in open abdominal surgeries in case reports or case series. We aimed to compare the effectiveness of ESPB and anterior Quadratus Lumborum block (QLB III) as a postoperative analgesic for open nephrectomy. Methods: Seventy five patients scheduled for open nephrectomy were randomly allocated into three equal groups (25 each); group (C) patients operated under general anesthesia while in (QLB and ESPB) groups, patients received general anesthesia followed by unilateral (QLBIII or ESPB) respectively, with 0.3–0.4 ml/kg of bupivacaine 0.25%. The primary outcome was the 24 h cumulative morphine given postoperatively. The secondary outcomes were the first rescue analgesic time, postoperative pain score, time to perform technique and sensory block coverage. Results: The 24 cumulative morphine consumption and first rescue analgesic time were significantly higher and shorter, respectively, in control group compared to the QLB and ESPB groups with no significant difference between interventional groups. VAS score at rest and during movement was significant higher in control group at all different timing measurements compared to the interventional groups. The block performing time was significant shorter in ESPB compared to QLB and the coverage of QLB extends from T8 to L2 and ESPB from T6 to T12. Conclusion: The ESPB is as efficient as QLB III to provide analgesia and decrease perioperative opioid consumption, taking into account the technically challenging and the time consuming of QLB III making ESPB a highly promising alternative for postoperative pain relief following open nephrectomy