Background: percutaneous nephrolihotomy (PCNL) is the first choice for treatment of single more than 2cm and multiple renal stones. The prone position is the classical position preferred by most surgeons. Then the supine position was developed for percutaneous nephrolithotomy. Objective: to compare between supine and prone PCNL in the management of renal stones regarding number of puncture, stone free rate, operative time, intraoperative and postoperative complications. Patients and Methods: the patients were selected, all having multiple stones, or stone size 2 cm or more. They were 30 patients divided into two groups, group (A) prone 15 patients and group (B) supine 15 patients. The study excluded patients with renal anomalies, uncontrolled coagulopathy, pregnancy, immunosuppression, and ages less than 10 years. Results: the study demonstrated a significant difference only in operation time which was (89.00±30.37) in prone group & (64.67±24.75) in supine group with p-value (0.023) between the prone and supine position, with shorter operation time in the supine than the prone. The study has also demonstrated that there is no statistically significant difference between the two groups as regarding to stone free rates, hospital stay, intraoperative, and postoperative complications. Conclusion: in patients with multiple renal stones, or stone size 2 cm or more, supine PCNL has proved to be superior to prone PCNL as regarding operative time. However, Urologists should be familiar with the differences in the positions and be able to use the method appropriate for each patient.