Purpose: We compared the safety and efficacy of percutaneous antegrade ureterolithotripsy with retrograde ureterolithotripsy for large impacted proximal ureter stones in a prospective randomized manner. Materials and Methods: A total of 91 patients with large impacted proximal ureteral stones, defined as stones > 1 cm in size located between the ureteropelvic junction and the lower border of the fourth lumbar vertebra, were prospectively randomized for antegrade (44) or retrograde ( 47) ureterolithotripsy. Failure of the procedure (conversion to an open procedure), intraoperative and postoperative morbidity, operative time, hospital stay, stone clearance at discharge home, and follow-up were analyzed in each group. Results: The main complications were bleeding (2.3%; 1 of 43) for the antegrade procedure and ureteral injury ( 2.3%; 1 of 44) for the retrograde procedure. Percutaneous antegrade ureterolithotripsy was associated with longer operative times (75.4 +/- 11.8 v 30.6 +/- 7.8 minutes; P = 0.001), longer hospital stay (6.3 +/- 0.5 v 2.1 +/- 0.4 days; P = 0.001), and a longer interval to return to normal activities ( 7.8 +/- 0.7 v 2.7 +/- 0.6 days; P = 0.001). Nevertheless, the percutaneous antegrade procedure had a higher stone-free rate both at discharge home (95.3% v 79.5%; P = 0.027), and 1 month post-procedure (100% v 86.4%; P = 0.026). Conclusions: Percutaneous antegrade ureterolithotripsy is a valuable treatment modality for impacted proximal ureteral calculi larger than 1 cm, and achieves higher stone-free rates than those of retrograde ureteroscopy with holmium: YAG laser lithotripsy. The drawbacks of the antegrade procedure are longer operative time and hospital stay.