Objectives: Percutaneous nephrolithotomy (PNL) is sometimes associated with complications, especially in patients with complex stones. Herein, we review our experience with PNL to determine the impact of percutaneous access number and location on success and complication rates. Patients and Methods: During a 2-year period, a total of 275 patients with a mean age of 42.3 ± 14.8 (range: 13–75) years underwent PNL. Stones were classified as simple in 51.6%, and complex (staghorn calculi or renal pelvis stones coexisting with caliceal stones) in 48.4%. Percutaneous access was done under C-armed fluoroscopy and the tract was formed with a high-pressure balloon dilation system. One single percutaneous access was sufficient in 210 (76.4%), while 2 accesses were utilized in 44 (16%), and ≧3 accesses in 21 cases (7.6%). Supracostal access was performed in 23 (8.4%) patients. Results: An overall success rate of 94.9% was achieved. Stone location, but not the access point location, was the major determinant for success, which was 99.3 and 90.2% in patients with simple and complex stones, respectively (p < 0.01). Significant complications included bleeding necessitating blood transfusion in 28 (10.2%), and hydropneumothorax in 2 (0.7%) patients. Bleeding was observed in 39.1 and 7.5% of patients managed with supracostal access, and subcostal access, respectively (p < 0.01). An increased number of access points significantly augmented the risk for bleeding. Bleeding was encountered in 7.6% of patients managed with 1 percutaneous access point, and in 18.5% of cases managed with ≧2 access points (p < 0.05). Hydropneumothorax occurred in patients with supracostal access. Conclusion: Supracostal access as well as multiple punctures may be needed especially in the management of complex stones, and the need for multiple access points and supracostal access significantly increases complication rates.