Staghorn stones are stones that fill the major part of the pelvicalyceal system. Despite remarkable change sin the management of urolithiasis due to advent of ESWL, PCNL, the special problem of the preferred approach to the management of staghorn calculi remains unsettled. Anatrophic nephrolithotomy is considered for management of staghorn stones with large volume and unfavorable collecting system anatomy. Patients and Methods: Forty five cases with large staghorn stones were included in this study. They were divided into two groups, First groups including 20 cases who were managed by anatrophic nephrolithotomy, Second group containing 25 cases who were managed by pyelolithotomy with multiple nephrotomies.Age ranged between 9 years and 75 years with mean of 44.9 ± 16.4 years, preoperative GFR ranged between 10 ml/min and 95 ml/min with mean of 40.25 ± 18.8 ml/min. Follow-up range between 3 and 60 months and mean 9.4 + 11.3 Results: Twelve patients (80%) were completely free from stones post operatively and at follow-up, 3 patients (20%) showed post-operative residuals with two of them (13.3%) with small <4 mm, peripheral stones requiring no further intervention. Ischaemia time ranged between 30 minutes and 90 minutes with mean of 66 + 17.4 minutes. GFR as measured by radioisotope studies showed almost no change between pre-operative mean 39.42 ml/min and at 3 months follow-up 39.43 ml/min with P-value 0.997. Serum creatinine also shows minimal drop between pre-operative mean 1.8927 mg/dl and at three months follows-up after surgery (mean 1.8667 mg/dl) with P-value 0.801. Conclusion: Large staghorn stones can be safely managed by surgery. Anatrophic nephrolithotomy and multiple nephrotomies are comparable to each other as regarding results, and either of them can be used for extraction of large staghorn stones.