The aim of this study was to analyze the pre- and intraoperative risk factors that affect the development of postoperative systemic inflammatory response syndrome (SIRS) after percutaneous nephrolithotomy (PCNL). Medical records on 317 adult patients with the complete data who underwent single-stage PCNL and followed at our center were retrospectively studied. Patients' data were collected through a database which was collected prospectively. All patients' vital signs were recorded hourly in the postoperative period and were divided into two groups as patients developing SIRS and not developing SIRS. There were 202 men and 115 women with a mean age of 48 ± 13.7 (range 19-82) years. There were 53 (16.7 %) in the SIRS and 264 (83.3 %) patients in the non-SIRS group. Preoperative positive urine cultures (UCs), intraoperative positive renal pelvic urine cultures (RPUCs), and stone cultures (SCs) were strongly correlated with the development of SIRS (p = 0.001). In the SIRS developers' group, preoperative UCs, intraoperative RPUCs, and SCs were positive in 33.9, 22.5, and 28.6 % of patients, respectively, but only 9.8, 3.3, and 4.2 % for the corresponding specimens in non-SIRS group. Positive preoperative UCs, intraoperative RPUCs, and SCs are important factors indicating the development of postoperative SIRS. Appropriately treated preoperative urinary infections may not prevent infected urine at PCNL. RPUCs and SCs may be the only way to identify the causative organism and direct antimicrobial therapy, so we recommend collecting RPUCs and SCs routinely to identify the offending organism and guide treatment.