Background and Purpose: Percutaneous nephrolithotomy (PCNL) for staghorn calculi is one of the more challenging endourologic procedures. Although excellent stone-free rates are universally reported in the literature, complication rates vary widely, especially related to the need for blood transfusion. The purpose of this study was to evaluate the outcomes of PCNL for patients with staghorn calculi in a large series of patients at a single, tertiary referral, endourologic stone center. Patients and Methods: Between July 1990 and December 2005, 1338 patients underwent PCNL for renal stone disease at our institution. Among this group, 509 procedures were performed for patients with a partial or complete staghorn calculus. Data analysis included procedure time, length of hospital stay, number of access tracts, transfusion rates, other early and late complications, and stone-free status. Results: Mean patient age was 53.8 years (range 4-84yrs). The average procedure time was 104 minutes. Sixteen percent of the cases needed multiple access tracts (range 2-5), with the lower calix being the most commonly used in 64.1%, followed by the upper calix in 18.5% and the middle calix in 17.4%. Various intracorporeal lithotriptors were used, including ultrasound, pneumatic, electrohydraulic, and holmium:yttrium-aluminium-garnet laser. The transfusion rate among this group was 0.8%. There was no statistically significant difference in transfusion rates (0.7%-1.2% P=0.24) or other major complications in patients who were treated with either a single tract or among those needing multiple tracts. Stone-free rates at hospital discharge and at 3 months follow-up were 78% and 91%, respectively. Conclusion: PCNL is a safe and effective procedure in the management of staghorn calculi, with outcomes similar to those reported for percutaneous management of smaller volume nonstaghorn stones. Attention to accurate tract selection and placement as well as possession of the full array of endourologic equipment are essential to achieving an excellent outcome.