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Although percutaneous nephrolithotomy has been recommended as the first-line treatment for renal stones larger than 2 cm, its major complication rate is not negligible and less invasive approaches are to be explored. Thanks to the recent advances in endoscopic technology, flexible ureteroscopy has become another option in this setting. Herein we report our most recent experience with flexible ureteroscopy for large renal stones. Between September 2008 and May 2011, 20 patients with renal stones ≥2 cm underwent a total of 28 procedures of ureteroscopy with holmium laser lithotripsy, using the Olympus URF-P5 and a ureteral access sheath. The number of procedures, operative time, stone-free rates, stone compositions and complications were evaluated. Stone-free status was defined as the absence of fragments or fragments of ≤4 mm. Mean stone size was 3.1 cm (range 2.0–5.0). The average number of procedures was 1.4. One, two and three procedures were required in 13, six and one patients, respectively. Overall, the stone-free rate was 90%. The stone-free rate for preoperative stone size of 2 to ≤4 cm and >4 cm was 100% (14/14) and 67% (4/6), respectively. No major intraoperative complications were identified. Postoperative high-grade fever was observed in three patients, including one patient who developed sepsis. All these patients were successfully treated conservatively. Our findings suggest that ureteroscopy represents a favorable option for selected patients with renal stones, especially those 2 to ≤4 cm in size.