Objectives: The aim of this study was to evaluate whether obesity could influence the success and safety of percutaneous nephrolithotomy (PCNL) performed in the supine position.Patients and Methods: This prospective cohort study included 664 patients who underwent supine PCNL between September 2008 and June 2023. Patients were stratified into two groups: obese (272 patients) and nonobese (392 patients). To minimize bias, a 1:1 matching was performed between the groups based on Guy's stone score, preoperative stone burden, and potential confounding variables. Procedural success was defined as the complete absence of stones on CT performed 3 months postoperatively. Safety was assessed by the incidence of overall, infectious, and hemorrhagic complications, with complications graded using the modified Clavien-Dindo classification.Results: The obese patient group showed a significantly higher prevalence of hypertension, diabetes mellitus, and higher anesthetic risk according to the American Society of Anesthesiologists' classification. However, the complexity of the cases and the surgical technique employed were compared between the two groups. In the univariate analysis, no significant differences were observed in success rates (p = 0.118), overall complications (p = 0.222), hemorrhagic (p = 0.104), or infectious complications (p = 0.326). After matching, a significant reduction in hemorrhagic complications was identified in the obese patient group (odds ratio 0.43; 95% confidence interval: 0.18-0.97; p = 0.027). However, obesity was not associated with an increased likelihood of overall (p = 0.093) or infectious complications (p = 0.869), nor did it affect procedural success (p = 0.219).Conclusions: Obesity should not compromise the success or safety of PCNL when performed in the supine position. On the contrary, it may offer a protective effect against hemorrhagic complications. These findings suggest that supine PCNL is a safe and effective surgical option for obese patients, and obesity should not be regarded as a contraindication when the procedure is otherwise indicated.