Rectal bleeding is frequently seen in patients undergoing transrectal ultrasound (TRUS)-guided multiple biopsy of the prostate, but is usually mild and stops spontaneously. We report what is believed to be the first case of life-threatening rectal bleeding following this procedure, which was successfully treated by endoscopic intervention through placement of three clips on the sites of bleeding. This case emphasizes endoscopic intervention associated with endoclipping as a safe and effective method to achieve hemostasis in massive rectal bleeding after prostate biopsy. Additionally, current data on the complications of the TRUS-guided multiple biopsy of the prostate and the options for treating fulminant rectal bleeding, a consequence of this procedure, are described.