We report 2 cases of catastrophic complications following routine transrectal ultrasound guided prostate biopsy. The first patient incurred near-fatal septic shock due to multi-resistant Escherichia coli. Due to the severity of his shock, he developed bilateral leg gangrene requiring amputations. The second patient incurred significant hemorrhage eventually requiring an emergent general anesthesia and surgical management to control hemorrhage after other measures failed. While rare events, these reports emphasize the caution needed for physicians who routinely order prostate biopsies.