Objectives:The aim of the present study was to assess the analgesic efficacy of IV ketamine injection inaddition to nephrostomy tract infiltration of ketamine – bupivacaine on postoperative pain relief after tubeless percutaneous nephrolithotomy (PCNL). Patients and Methods: Patients (n = 100), with renal stone who were candidates for PCNL were randomized to five groups with 20 cases in each: Group C, 10 mL of saline solution was infiltrated into the nephrostomy tract; Group B, 10 ml of 0.25% bupivacaine was infiltrated into the nephrostomy tract; Group BK1, 10 ml of 0.25% bupivacaine plus 0.5mg/kg ketamine was infiltrated into the nephrostomy tract; Group BK2, 10 ml of 0.25% bupivacaine plus 1.5mg/kg ketamine was infiltrated into the nephrostomy tract; Group K, 10 ml of saline solution containing 0.5mg/kg ketamine was intravenously administered. Post-operative pain scores were compared between groups as the primary objective. Comparison of Sedation Scores, rescue analgesic consumption, time to the first rescue analgesics administration, hemodynamic and SpO2 values were regarded as the secondary objective. Results: Mean VAS scores in the first 30 minutes and total analgesic consumption in the first 24 hours of post-operative period were significantly lower in groups BK1 and BK2 in comparison with the other groups (P < 0.05). Also, time to first rescue analgesics administration was longer in the same groups (P < 0.05). Conclusions: Infiltration of ketamine plus bupivacaine provides superior analgesic effects in PCNL surgery compared with other methods.