• Background:Prostate cancer is the most common malignancy among men globally, with a higher incidence in older males. The increasing aging population exacerbates the burden of this disease. Transperineal prostate biopsy under ultrasound guidance is considered the "gold standard" for diagnosis; however, patients often experience significant pain, adverse emotions, and severe stress reactions during the procedure, particularly elderly patients. An ideal anesthetic regimen, in line with the principles of ERAS, should be characterized by rapid onset, short duration, hemodynamic stability, minimal respiratory depression, and swift recovery. This study investigates the differences in anesthetic efficacy and recovery quality between remimazolam and etomidate in elderly patients undergoing prostate biopsies. Although etomidate is commonly used in elderly patients due to its hemodynamic stability, its metabolism is dependent on liver and kidney function, and it has multiple limitations including poor controllability, adrenal suppression, muscle twitching, injection pain, and prolonged recovery time. In contrast, remimazolam offers rapid onset, short half-life, minimal respiratory depression, low incidence of nausea and vomiting, and can be quickly reversed with flumazenil, potentially leading to more predictable recovery times and fewer adverse reactions. • Methods: This study involved the administration of total intravenous anesthesia in elderly patients undergoing prostate biopsy, utilizing sufentanil for analgesia, followed by either etomidate or remimazolam for sedation. Flumazenil was administered at the end of the procedure to reverse the effects of remimazolam. The primary outcome was to compare the recovery time and quality of recovery in patients receiving remimazolam with those receiving etomidate. • Discussion: This study aims to conduct a randomized controlled study to systematically evaluate the efficacy (anesthetic recovery and quality) and safety (haemodynamic/respiratory events and adverse reactions) of these etomidate and remimazolam-flumazenil in elderly patients undergoing transperineal prostate biopsy. thereby enhancing patient comfort and satisfaction during medical care. • Trial registration: The registration number: Chinese Clinical Trial Registry (ChiCTR2400091993).Date of registration: 24 October 2024