Background: Postoperative pain management is critical for patients undergoing percutaneous nephrolithotomy (PCNL). Effective analgesia enhances recovery, reduces hospital stays, and improves patient satisfaction. The posterior quadratus lumborum block (QLB) and the erector spinae plane (ESP) block are two regional anesthesia techniques gaining popularity. This study aims to compare the efficacy of these blocks in providing postoperative analgesia for PCNL patients, focusing on the advantages of the ESP block. Methodology: In this randomized controlled trial, 126 patients scheduled for PCNL were divided into two groups: Group A received the PQL Block, while Group B received the ESP block. Both blocks were performed under ultrasound guidance using 15 ml of 0.25% Ropivacaine. All patients received postoperatively opioid (Tramadol 50 mg), with 4- 5 patients in Group A receiving 100 mg. Pain intensity was assessed using the Visual Analog Scale (VAS) at 30 min,1, 3, 6, 12, and 24 hours postoperatively. Secondary outcomes included total opioid consumption, time to first analgesic request, and incidence of side effects. Results: Group B (ESPB) demonstrated significantly lower VAS scores at all postoperative time points compared to Group A (QLB) (p<0.05). The time to first analgesic request was longer in Group B (12.1 ± 2.8 hours) than in Group A (9.3 ± 2.5 hours) (p<0.05). Total opioid consumption was also lower in Group B (60 ± 10 mg)compared to Group A (80 ± 15 mg) (p<0.05). Additionally, Group B reported fewer side effects, including nausea and sedation, enhancing overall patient comfort and satisfaction. Conclusion: The erector spinae plane block provides superior postoperative analgesia compared to the posterior quadratus lumborum block in patients undergoing percutaneous nephrolithotomy. The ESP block resulted in lower pain scores, reduced opioid consumption, prolonged analgesia, and fewer side effects. These findings suggest that the ESP block is a more effective and safer regional anesthesia technique for managing postoperative pain in PCNL patients.