OBJECTIVE We compared the safety and efficacy of percutaneous antegrade ureterolithotripsy with retrograde ureterolithotripsy for large impacted proximal ureter stones in a prospective randomized manner. 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.