Three male physicians underwent transrectal ultrasound guided prostate biopsies for elevated prostate-specific antigen levels or irregular digital rectal exam findings. All three of these patients developed urosepsis secondary to multi-drug resistant organisms despite antibiotic prophylaxis. There are increasing reports of infectious complications following prostate biopsy caused by multi-drug resistant organisms. These cases highlight the potentially lethal risks to healthcare workers who are more likely to harbor multi-drug resistant organisms than the general population. Further research into preoperative assessment and appropriate antibiotic prophylaxis in all potentially high risk patients is warranted.