Introduction: Current guideline recommends percutaneous nephrolithotomy as a procedure of choice having stone size larger than 2 cm, infected stones, lower calyceal stones and in patients in whom shock wave lithotripsy has failed. The pneumatic and ultrasonic lithotripsy devices can be used alone or in combination (pneumatic + ultrasonic). These two systems work through different mechanisms but possess different advantages and disadvantages in practice. Objective: To compare the operative outcomes (e.g. operation time, stone clearance rate and hospital stay) in patients treated with combined pneumatic lithotripsy plus ultrasonic lithotripsy versus pneumatic lithotripsy alone for the management of staghorn renal calculi. Study Design: Randomized Clinical Trial. Setting: The study was completed at Sindh Institute of Urology and Transplantation Karachi, Pakistan. Duration of Study: 8th, Feb 2017 to 7th, Aug 2017.Patients and Methods: A total number of 66 patients with diagnosis of staghorn calculi, who were plan for PCNL, were included in this study. Patients were divided into two equal groups. Group I: Patients underwent combined use of pneumatic plus ultrasonic lithotripsy for the treatment of renal stones and Group II patients underwent pneumatic lithotripsy alone. Operation time, hospital stay and stone clearance was noted in all patients. Data analysis was carried out using SPSS v20.0. Chi-square test was used to compare outcome result between groups. Independent sample t-test was used for comparison of operation time and hospital stay time between the groups. Results: The mean age of the patients was 49.83+9.06 years. There were 42 (63.6%) males and 24 (36.4%) females. There were 50 (75.8%) patients who presented with partial staghorn stones and 16 (24.2%) patients were presented with complete staghorn stones. Stone clearance rate was 87.9% in group I and 81.8% in group II patients with a p-value of 0.49. The mean operation time was 190.72+17.15 minutes in group I and 225.09+18.49 in group II (p-value <0.001). The hospital stay time was 3.48+1.00 days in group I and 4.45+1.37 days in group II (p-value 0.002). Conclusion: The combination of ultrasonic lithotripter and pneumatic lithotripter is more effective than pneumatic lithotripter alone because it significantly decreases operative time hospital stay and increases stone clearance rate. Keywords: Staghorn stones, pneumatic lithotripsy, ultrasonic lithotripsy