Introduction: The use of percutaneous nephrolithotomy (PCNL) in obese patients with nephrolithiasis has been a subject of debate. Numerous publications have debated the pros and cons of this procedure. In order to assess the efficacy and feasibility of this technique in patients with a BMI>25 kg/m2, several factors should be studied and compared. Purpose: The purpose of this study is to prove the efficacy and safety of prone PCNL in obese patients and to compare preoperative, intraoperative and postoperative variables between obese patients and those with normal BMI. Methods: Data was collected throughout 7 years on all patients presenting for PCNL at our institution. All patients underwent prone PCNL under fluoroscopy by a single urologist and the need for subsequent procedure was studied. A total of 276 patients were grouped, after applying exclusion criteria, into 4 categories according to their BMI: Normal BMI (72), overweight (112), obese (80) and Morbidly Obese (12). Using statistical analysis data was compared among the 4 groups of BMI. Results: The risk of intraoperative related complications including pneumothorax and bleeding was the same among the 4 study groups (p=0.07). No difference was found in terms of subcostal v/s intercostal access (p=0.068). 8%, 1.79%, 8.54% and 0% of the normal, overweight, obese and morbidly obese respectively required transfusions (p=0.103). No significant difference (p=0.07) was found among the groups in overall complication rates being 12% in the Normal BMI group,16% in the overweight, 10% in the obese, and 21% in the morbidly obese. Mean operative time was 84.39, 85.45, 97.31 and 122.5 min in the normal, overweight, obese and morbidly obese respectively (p=0.01). Stone free rate was 52% in the normal BMI group, 62% in the overweight, 66% in the obese and 50% in the morbidly obese (p=0.268). Conclusion: PCNL in obese patients, BMI>25 kg/m2, was associated with a longer operative time, but with similar rate of complications, transfusion requirements and the need for subsequent procedures when compared to patients with normal BMI. This pioneer study in the Middle East establishes PCNL as safe and feasible procedure in obese patients.