We evaluated the impact of intraoperative irrigation pressures on the risk of systemic inflammatory response after percutaneous nephrolithotomy.Between January 2014 and March 2015, 90 patients with renal stones planned for percutaneous nephrolithotomy were randomized between low (80 mm Hg) and high (200 mm Hg) irrigation pressure. Patient demographics, perioperative outcomes and systemic inflammatory response incidence rates were compared using the chi-square and Wilcoxon signed rank tests.Mean patient age, gender, body mass index and other perioperative outcomes were similar in both arms. High pressure irrigation was associated with a higher risk of systemic inflammatory response syndrome (46%) compared to low pressure irrigation (11%, p=0.0002). On multivariate analysis only high irrigation pressure, paraplegia or neurogenic bladder and nonquinolone perioperative medication were predictive of postoperative systemic inflammatory response syndrome.High pressure fluid irrigation fluid increases the risk of postoperative systemic inflammatory response syndrome after percutaneous nephrolithotomy.