To assess the efficacy and safety of high-power holmium-yttrium-aluminum-garnet (YAG) laser lithotripsy for percutaneous nephrolithotomy in patients with large renal stones. We retrospectively reviewed the charts of 87 patients who underwent 91 percutaneous nephrolithotomy procedures at our hospital from April 2004 to June 2005, during which a holmium-YAG laser with a self-made fiber guider was used for lithotripsy. Of the 91 procedures, 51 were performed with the maximal power output set at 3.0 J in patients with a renal stone size of 3 cm or larger (group 1). The other 40 procedures were performed with the maximal power set at 2.0 J in patients with a renal stone size of less than 3 cm or with ureteral stones (group 2). The average stone size was 5.4 cm in group 1, and the stone-free rate was 61.4% after a single procedure. The average operation time was 108 minutes in group 1 and 93 minutes in group 2. The average postoperative hospital stay was 5.7 days in group 1 and 5.9 days in group 2. Two patients in group 1 and one in group 2 required blood transfusions after the procedure. Seven patients (13.7%) in group 1 and two (5.0%) in group 2 experienced a urinary tract infection after the procedure. No statistically significant difference in procedure time, postoperative hospital stay, blood transfusion rate, or postoperative urinary tract infection rate was found between the two groups. The results of our study have shown that using a high-power holmium-YAG laser is safe and effective in the treatment of large renal stones.