OBJECTIVE: To compare the efficacy and safety of regional epidural anesthesia and general anesthesia in patients who underwent PCNL. MATERIALS AND METHODS: Fifty patients submitted to percutaneous nephrolithotomy (PCNL) were randomized into two groups: Group I (N = 26) received general anesthesia and Group II (N = 24) received regional epidural anesthesia. Demographic and operative data including age, BMI, stone position, stone size, postoperative pain, amount of postoperative analgesic usage, length of hospital stay, patient satisfaction, preoperative and postoperative hemoglobin and hematocrit, adverse effects and surgical complications were compared between both groups. RESULTS: Average pain score at 1 hour. was 6.88 in group I and 3.12 in group II (p < 0.001), at 4 hours. 5.07 in group I and 3.42 in group II (p = 0.025). Less morphine was required in the regional epidural anesthesia group compared to the general anesthesia group. Higher satisfaction was found in the regional epidural group. 6 (23.07%) patients in Group I and 1 patient (4.19%) in Group II had postoperative nausea and vomiting, respectively (p = 0.05). Pain score at 12 hours, 24 hours, 48 hours, 72 hours, preoperative and postoperative hemoglobin and hematocrit, length of hospital stay, and adverse effects were no different between the two groups. CONCLUSION: Regional epidural anesthesia is an alternative technique for PCNL which achieves more patient satisfaction, less early postoperative pain and less adverse effects from medication with the same efficacy and safety compared to general anesthesia.