Background: The Quadratus Lumborum Block (QLB), which is reported to provide analgesia to the abdominal region, is a newly defined fascial plane block method. The present study aimed to investigate the effect of ultrasound guided anterior QLB on the postoperative pain scores after percutaneous nephrolithotomy. Methods: In this prospective, randomized, controlled single-blind study, 60 patients with elective percutaneous nephrolithotomy operations were randomized into 2 groups. In Group B (n = 30): anterior QLB+ intravenous patient-controlled analgesia (PCA) morphine and in Group C (n = 30): intravenous PCA morphine. Outcome measures were included for visual analog scale (VAS) scores and morphine consumption for 24 hours postoperatively. Adverse effects, additional analgesic requirement, and intraoperative opioid requirement were recorded. Results: The mean values of the quantity of morphine used at the 6th, 12th, and 24th hours were found to be statistically significantly lower in Group B (p < 0.05). The VAS scores were found to be statistically significantly lower in Group B (p < 0.05). There were no statistically significant differences in the rate of adverse effects, additional analgesic requirement, and intraoperative opioid requirement between the groups (p > 0.05). Conclusion The study results suggest that anterior QLB is an effective treatment option for postoperative analgesia of percutaneous nephrolithotomy.