A human immunodeficiency virus-infected man who has sex with men presented with several months of abdominal pain, diarrhea, rectal pain, and rectal discharge of bright red blood and pus. He reported receptive anal intercourse with multiple casual male partners. He was subsequently diagnosed with lymphogranuloma venereum proctitis and Clostridium difficile colitis. It is possible that C. difficile was sexually transmitted in this case because the patient did not have any of the traditional risk factors for C. difficile. Clinicians should be cognizant of the diagnosis of lymphogranuloma venereum, particularly among high risk men who have sex with men, and its potential association with other gastrointestinal pathogens such as C. difficile that may be sexually transmitted. Failure to identify and treat these pathogens can lead to significant complications and the potential for transmission to others. Copyright © 2014 by Lippincott Williams &Wilkins.