Purpose: The cost-effectiveness of shock wave lithotripsy monotherapy, percutaneous nephrolithotomy and combined sandwich therapy in the treatment of staghorn calculi was examined. Materials and Methods: The cost-effective index, which estimates the average cost of making 1 patient stone-free, was computed for the various treatment options. Data for effectiveness of each therapy were used as available from the literature. Billing charges were used as cost data from University Hospital and the Kidney Stone Center. Results: Average charges for a single percutaneous nephrolithotomy were $26,622, of which 81% were facility charges and 7.9% urologist fees. Average charges for a single shock wave lithotripsy were $8,213, 60.3% of which were facility fees and 33.3% of which were urologist charges. Overall, percutaneous nephrolithotomy and combined sandwich therapy were more cost-effective than shock wave lithotripsy monotherapy. When the stone surface area was less combined sandwich therapy and shock wave lithotripsy monotherapy were than 500 mm.(2) equally cost-effective. However, when the stone burden was greater than 500 mm.(2) combined sandwich therapy clearly became more cost-effective than shock wave lithotripsy monotherapy. Conclusions: Percutaneous nephrolithotomy followed by shock wave lithotripsy, if necessary, and second look nephroscopy are the most cost-effective methods of treating staghorn calculi.