Objectives: To identify perioperative risk factors for postoperative systemic inflammatory response syndrome (SIRS) and suggest possible modifications to reduce morbidity. Material and Methods: We prospectively analysed perioperative data such as history of pervious stone surgery, number and configuration of stones, presence of stent or nephrostomy, any previous positive urine culture, intraoperative renal pelvic urine and stone culture, aspiration of turbid urine on initial puncture, number of tracts required and clearance of stones, operative time and intraoperative hypotension and tachycardia of all patients who underwent percutaneous nephrolithotomy over a period of 15 months. Results: A total of 182 patients were included, average stone size was 2.8 cm, 36.2% had staghorn stones and 15.9% had an indwelling stent or nephrostomy. Despite sterile preoperative urine culture, renal pelvic urine culture (RPUC) was positive in 14.8% (27 patients) and stone culture was positive in 21.9% (40 patients). SIRS developed in 17.5% (32 patients) and septic shock in 1.09% (2 patients). On analysis younger age, positive RPUC and stone culture, longer operative time and intraoperative tachycardia correlated significantly with the development of SIRS. Conclusion: Intra-operative cultures are only therapy-guiding cultures during SIRS, as preoperative urine cultures seldom accurately depict bacteriological status of upper tracts and thus should be obtained in all patients.