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Percutaneous nephrolithotomy is generally performed using fluoroscopy, which is associated with exposure to radiation. Another drawback of fluoroscopic guided percutaneous nephrolithotomy is the prone position, which is not suitable for all patients. In this study we evaluated the feasibility, safety and efficacy of ultrasound guided percutaneous nephrolithotomy with the patient in the flank position.A total of 603 patients with a mean ± SD age of 50.9 ± 13 years were included in this study from December 2010 to July 2016. Access to the collecting system and tract dilation were performed under ultrasound guidance. Perioperative data on the stone-free rate, operative time, length of stay and complication rates were recorded.Successful access was achieved in all but 1 patient. Mean operative time was 56.6 ± 6.5 minutes. Complete stone clearance was achieved in 529 patients (87.7%) and Clavien-Dindo grade 3 complications were noted in 17 (2.8%). Blood transfusion was necessary in 43 patients (7.1%). However, bleeding was self-limited in all cases and did not require angioembolization.To our knowledge this is the largest series of ultrasound guided percutaneous nephrolithotomy with the patient in the flank position. Unlike in other studies we used this procedure in all patients irrespective of stone burden, renal anomaly and body habitus. Ultrasound guided percutaneous nephrolithotomy has outcomes comparable to those of conventional percutaneous nephrolithotomy and it is not associated with radiation exposure. Furthermore, anesthesia while in the flank position might be less harmful in some patients, including those with obesity or cardiopulmonary comorbidities.