Ureterorenoscopy (URS) is a common minimally invasive diagnostic and therapeutic modality for ureteral and renal pathology. Fluid absorption during routine URS has not been studied prospectively, despite the fact that fluid absorption during other endoscopic urologic procedures can be substantial. During URS in 15 male and 8 female patients with a mean age of 54 years (range 19-81 years), volumetric balance was performed by measuring all fluids instilled into the urinary tract (irrigation fluid and contrast medium) and fluids collected from the urinary tract (irrigation fluid, contrast medium, and urine output) and by estimating urine output from creatinine concentration in the urine and in the fluids collected from the urinary tract. Fluids from the urinary tract were assessed by measuring drainage fluid and the preoperative and postoperative weights of the drapes and bedsheets. Of the procedures, 11 were right-sided and 12 were left-sided. The indications for URS were urolithiasis (N = 18) and diagnosis (hematuria in 2, ureteral or renal filling defect in 2, flank pain and hydronephrosis in 1). The mean total operative time was 55 minutes (range 20-95 minutes), and the mean URS time was 37 minutes (range 8-83 minutes). The mean volume of irrigation fluid used was 2531 mL (range 552-5580 mL). The mean estimated urine output during the procedure was 62 mL (range 7-201 mL). The mean estimated systemic fluid absorption during URS was 54 mL (range 4-137 mL). There were two intraoperative complications (ureteral perforations) but no postoperative complications. Routine URS is associated with minimal systemic fluid absorption, even if ureteral perforation occurs. Estimated absorption of as much as 137 mL was seen; however, evaporative losses and unaccounted-for losses of fluid likely account for a substantial portion of this fluid discrepancy. This result suggests that irrigation with fluids other than normal saline, such as sterile water, during URS is likely safe.