BACKGROUND: Percutaneous nephrolithotomy is one of the preferred treatment options for upper urinary tract stones. However, postoperative bleeding remains a clinical challenge. It is crucial to identify the effectiveness of this procedure and understand the risk factors causing postoperative bleeding. METHODS: A total of 383 patients with upper urinary tract stones included in our hospital from March 2020 to February 2024 were retrospectively selected and divided into 2 groups as per different treatments. A total of 204 patients who underwent guidewire-assisted percutaneous nephrolithotomy were included in the guidewire-assisted group, while the other 179 patients who underwent conventional percutaneous nephrolithotomy were enrolled in the conventional group for a comparison of treatment effects. Then, single-factor and multifactorial logistic regressions in accordance with the postoperative bleeding situation were conducted to analyze the risk factors of postoperative bleeding in patients with upper urinary tract stones. RESULTS: The results showed that the guidewire-assisted percutaneous nephrolithotomy group had a higher stone removal rate compared to the conventional group, with lower rates of complications, operation time, gastrointestinal recovery time, hospital stay, postoperative bleeding, and hemoglobin drop ( CONCLUSION: Compared to conventional percutaneous nephrolithotomy, guidewire-assisted percutaneous nephrolithotomy could improve the stone removal rate of patients with upper urinary tract stones and reduce the occurrence of complications, while some patients were still prone to the postoperative bleeding phenomenon, which might be closely related to the preoperative Scr, surgical methods, hydronephrosis, and renal parenchymal thickness. The mentioned phenomenon needed clinical attention and corresponding measures to intervene as soon as possible to reduce the bleeding in the postoperative period.