Objective This study was designed to evaluate the aspects that affect transfusion following percutaneous nephrolithotomy (PCNL). Patients and Methods. From 2016 to 2019, 665 patients underwent PCNL for the removal of renal calculi at our center (Department of Urology, Shanghai Xu-hui Central Hospital). Complications, including hemorrhages, have been reported. Twenty-three patients (3.5%) have received a blood transfusion, and 12 (1.9%) patients were treated with hyper-selective embolization. We focused on the influencing factors related to postoperative blood transfusion. The factors analyzed were age, sex, hypertension, diabetes, serum creatinine level, preoperative hemoglobin, and the use of anticoagulants or antiplatelet medications; renal and stone factors (i.e., previous surgery, abnormal anatomy, stone side, stone burden, and stone type); and surgical features (i.e., access number, the calyx of puncture, and stone-free rate). These data were analyzed for the presence of bleeding. Results Among individual factors, preoperative hemoglobin level (p < 0.001) and urinary infections (p < 0.001) were significantly correlated with blood transfusion. Among renal and stone factors, only a history of open surgery was significantly correlated with blood transfusion (p < 0.05). Stone type or stone burden did not correlate with transfusion. Furthermore, no statistically significant correlation was found between surgical features and bleeding, and a lower stone-free rate was reported for the transfusion group. Conclusion The obtained results demonstrated that PCNL is a safer surgical procedure in a high-volume center; however, anemic conditions, infections, and history of open surgery will significantly increase the transfusion rate following PCNL.