Aims: To investigate whether deep sedation for transrectal prostate biopsy could reduce anxiety and pain and enhance rebiopsy compliance. Methods: A two-centre prospective observation study was conducted under two different anaesthetic conditions: deep sedation with analgesia and local anaesthesia with lidocaine. A 12-core prostate biopsy was taken in all patients. Scores on a 0-10 visual analogue scale, the State-Trait Anxiety Inventory-X-1, the Beck Anxiety Inventory and a five-level Likert satisfaction scale were evaluated. Finally, all patients were asked about their willingness to undergo the same procedure again if necessary and whether they wanted to change the anaesthetic method (deep sedation to local anaesthesia or local to sedation) if a repeat procedure was required. Results: A total of 135 patients were included in this study, including 69 patients in the sedation group and 66 patients in the local group. Lower pain scores (P <.001) and higher satisfaction scores (P =.019) were observed in the sedation group than in the local group after the procedure. Anxiety scores in the sedation group were significantly decreased after the procedure, whereas those were not changed in the local group. The question regarding rebiopsy compliance tended to be more positive in the sedation than in the local group (73.9% vs 62.1%, respectively, P =.099). The proportion of patients who wanted to change their anaesthetic method was much higher in the local than in the sedation group (68.2% vs 11.6%, respectively, P <.001). Conclusion: Deep sedation with analgesia during transrectal prostate biopsy could reduce pain and postprocedural anxiety and enhance rebiopsy compliance. Considering the psychological and oncological benefits, we strongly recommend inducing deep sedation during transrectal prostate biopsy.