Objectives <p>To assess whether advanced age influences the safety and efficacy of percutaneous nephrolithotomy (PCNL) performed in the supine position.</p> Methods <p>We conducted a prospective cohort study including 714 renal units treated with supine PCNL at a single tertiary center between October 2008 and October 2024. Patients were categorized into two groups: &lt;80 years (<i>n</i> = 672) and ≥ 80 years (<i>n</i> = 42). To reduce selection bias, a 1:1 propensity score-matched analysis was performed based on Guy’s stone score, preoperative stone burden, and potential confounders. Procedural success was defined as the absence of residual stones on computed tomography (CT) at three months postoperatively. Safety outcomes included overall, infectious, and hemorrhagic complications, classified according to the modified Clavien-Dindo system.</p> Results <p>Octogenarians had a significantly higher prevalence of hypertension, diabetes mellitus, antiplatelet or anticoagulant therapy, higher American Society of Anesthesiologists (ASA) scores, and positive preoperative urine cultures. Case complexity and surgical technique were comparable between groups. In univariate analysis, there were no significant differences in overall (<i>p</i> = 0.242), hemorrhagic (<i>p</i> = 0.450), or infectious (<i>p</i> = 0.702) complications. The stone-free rate was higher in patients aged ≥ 80 years in the univariate analysis (<i>p</i> = 0.004), but the difference did not remain significant after adjustment (<i>p</i> = 0.085). In the matched cohort, advanced age was not associated with higher odds of overall (<i>p</i> = 0.358), hemorrhagic (<i>p</i> = 0.233), or infectious complications (<i>p</i> = 0.453).</p> Conclusions <p>Our findings provide further evidence supporting that supine PCNL is safe and effective in the elderly when clinically indicated.</p>