© 2015. Percutaneous nephrolithotomy (PCNL) is a minimally invasive procedure for patients with large renal and upper ureteric stones. Although it is less invasive than open surgery, infection is still the most common complication arising from this procedure and some patients develop septicemia and septic shock, resulting in increase in mortality and morbidity. The incidence of septic shock following PCNL is 1%; however, its mortality rate is as high as 66-80%. Endourologists who perform this procedure need to know how to prevent and manage this common complication. Large calculi, staghorn calculi, positive pelvic urine and stone culture, prolonged operative time, and diabetes are factors that increase the incidence of postoperative infection. Recently, several studies suggested the importance of intraoperative microbiologic evaluation of factors such as intraoperative pelvic urine and stone cultures for selection of suitable postoperative antibiotics. The selection of prophylactic antibiotics, postoperative antibiotics, and specific PCNL techniques play an important role in preventing infection following PCNL. We reviewed the general background, the factors, and role of intraoperative microbiologic evaluation in the management of post-PCNL infection.