Purpose Percutaneous nephrolithotomy (PCNL) is performed commonly in patients with large kidney stones, but the management of their postoperative pain presents a major challenge. While it is not routinely performed in PCNL patients, paravertebral block (PVB) has been described as an effective strategy for pain control after various non-urologic surgeries. This trial aims to assess the effect of paravertebral blockade on intraoperative and postoperative opioid use as well as postoperative pain control in patients undergoing PCNL. Methods This was a prospective, randomized, double-blind, placebo-controlled study. Patients who consented to participate were randomly assigned to undergo either PVB or a placebo intervention preoperatively. The patient, surgeon, and anesthesia team were all blinded to the randomization. The outcome parameters were intraoperative opioid requirement, postoperative visual analog scale (VAS) pain scores, postoperative opioid use, and postoperative antiemetic use. Results 23 patients were enrolled in each arm of the study, and the two groups had no significant differences in baseline demographic or clinical characteristics. Patients in the PVB group had significantly lower intraoperative opioid use, postoperative opioid use, frequency of opioid use, and antiemetic. Patients in the PVB group also had lower postoperative VAS pain scores. There were no patients who suffered from complications attributable to PVB. Conclusion The results of this randomized, double-blind, placebo-controlled trial suggest that PVB should be considered an effective strategy to reduce opioid requirement and improve pain control for patients undergoing PCNL.