Abstract Objective Infectious complications (IC) following percutaneous nephrolithotomy surgery (PCNL) can be life-threatening. Our objective was to analyze preoperative predictors of IC in PCNL. Materials and methods A total of 203 patients who underwent PCNL were included in a prospective study between January 2013 and February 2016. A postoperative IC was defined as urinary infection/pyelonephritis, systemic inflammatory response syndrome or sepsis. The variables analyzed were age, gender, number, size (cm) and side of stone; Hounsfield units, diabetes (insulin dependent or not), preoperative culture, isolated bacteria, multitract, body mass index and surgical time (min). A multivariate forward stepwise (logistic regression) was performed. Results IC occurred in 30 patients (14.8%): 9 (4.4%) had urinary infection, 14 (6.9%) systemic inflammatory response syndrome and 7 (3.5%) sepsis. In addition, 13 (43.3%) had negative preoperative urine culture, 15 (50%) positive and in 2 (6.7%) was not available. On the logistic regression analysis, stone size (cm), insulin dependent diabetes and female sex were independently associated with increased risk of IC (odds ratio [OR] 1.03, 14.6 and 7.8, respectively; p = 0.0001). Conclusions Patients with large stone burdens, insulin–dependentdiabetes condition and female gender, should be counselled properly regarding postoperative infection risks and closely followed up to diagnose IC (specially sepsis) soon enough. Negative preoperative urine culture seems not reliable enough to exclude an infectious complication according to our results.