Purpose: Uroseptic shock is a life threatening complication after upper urinary tract endoscopic lithotripsy. Prompt diagnosis and treatment are paramount for patient survival. We identified a practical predictor of upper urinary tract endoscopic lithotripsy induced uroseptic shock in an animal model. We validated the results by retrospectively reviewing multicenter clinical records. Materials and Methods: We ligated the rabbit ureter and injected Escherichia coli solution in the renal pelvis to create a uroseptic shock model. White blood count and other parameters were measured at different intervals and bacterial concentrations. Results were compared with clinical findings in 48 patients who experienced uroseptic shock after upper urinary tract endoscopic lithotripsy at a total of 8 medical centers. We used a ROC curve to evaluate the predictive value of parameters for uroseptic shock. Results: We established a stable rabbit model by injecting 9.0 x 10(8) cfu/ml E. coli in the renal pelvis at a dose of 2 ml/kg. In patients and rabbits with uroseptic shock the white blood count decreased in the first 2 hours after the procedure. The ROC curve showed that the white blood count threshold within the first 2 hours of uroseptic shock was 2.85 x 10(9)/L. Sensitivity and specificity for predicting uroseptic shock were 95.9% and 92.7%, respectively. Conclusions: The white blood count decreased drastically within the first 2 hours during the development of uroseptic shock. This could be an ideal predictor of uroseptic shock after upper urinary tract endoscopic lithotripsy. In patients with high risk factors for uroseptic shock the white blood count should be measured within 2 hours after upper urinary tract endoscopic lithotripsy.