Percutaneous nephrolithotomy (PCNL) is considered the treatment of choice for large urinary calculi and staghorn lithiasis. The approach for this surgery may be either supine or prone, and different access techniques are described in the literature with the use of ultrasound, fluoroscopy, or both combined. We believe that prone PCNL offers to the urologist key advantages, such as the possibility of puncturing anatomically abnormal urinary tracts, to perform multiple percutaneous tracts in the same kidney, experiencing the vacuum cleaner effect, ease of exploring the upper calyx through the inferior calyx, possibility to perform endoscopic combined intrarenal surgery (ECIRS) and bilateral simultaneous surgery, and to performed over local anesthesia. An adequate training for the endourologist should include both the prone and supine techniques for PCNL and to know which patient can benefit the most from each one.