Objective: To examine the effectiveness and safety of application of the ureteral access sheath in the treatment of middle or lower ureteral calculi in patients with large-volume benign prostatic hyperplasia above grade Ⅲ, which is expected to avoid the simultaneous or staged treatment of benign prostatic hyperplasia via eliminate the difficult angle and resistance of ureteroscopy caused by severe prostatic hyperplasia. Methods: From April 2018 to December 2020, the clinical data of 27 patients with massive benign prostatic hyperplasia above grade Ⅲ and middle and lower ureteral calculi treated with indwelling ureteral access sheath plus ureteroscopy holmium laser lithotripsy at Department of Urology, Zhejiang Quhua Hospital were retrospectively analyzed and followed up. All the patients were male, aged (69.7±12.8) years (range: 55 to 87 years). Prostate volume measured by transrectal ultrasound was (94.8±16.2) cm3 (range: 85 to 186 cm3). The ureteral access sheath was indwelled in advance, and then the semirigid ureteroscopy was introduced through the working channel of the sheath. Holmium laser lithotripsy was performed, and intraoperative and postoperative complications were recorded. Urinary abdominal plain X-ray or CT urography were performed at 1-and 2-month postopaerative to evaluate the residual stones and clinical efficacy. Results: The ureteral access sheath was placed and holmium laser lithotripsy under a semirigid ureteroscopy was performed successfully in all the 27 patients. In 2 patients, a second session of auxiliary procedure was required due to the large load of preoperative stones and residual stones after surgery, among whom 1 patient received extracorporeal shock wave lithotripsy and 1 patient underwent extracorporeal shock wave lithotripsy plus ureteroscopic lithotripsy. The stone free rate at 1-and 2-month postoperative were 92.6% (25/27) and 100% (27/27), respectively. There were no severe complications such as ureteral avulsion and perforation, perirenal hematoma, septic shock, severe hematuria, urinary retention, iatrogenic ureteral stricture occurred during and after the surgery. The ureteral calculus was wrapped by polyps heavily in 1 patient, he was diagnosed as ureteral stenosis 1 month postoperative, receiving laparoscopic resection of ureteral stricture plus anastomosis 3 months postoperative. Conclusions: In the operations of middle and lower ureteral calculi in patients with large-volume prostatic hyperplasia above grade Ⅲ, the ureteral access sheath can be placed first to effectively eliminate the difficult angle and resistance of ureteroscopy caused by severe prostatic hyperplasia, and then semirigid ureteroscopic lithotripsy can be safely performed. It could avoid the treatment of benign prostatic hyperplasia at the same time or by stages.