Clostridium difficile ( C. difficile ) is a cytotoxin-producing anaerobic gram-positive rod that is responsible for pseudomembranous colitis (PMC). The incidence of C. difficile is increasing in ulcerative colitis (UC) and inflammatory bowel disease patients and is associated with a more severe course, a longer hospital stay, higher financial costs, a greater likelihood of colectomy, and high mortality. PMC may occur anywhere along the intestinal tract, but it is often found in the distal colon. PMC involving the proximal colon with rectosigmoid sparing is rarely reported in patients with UC. We describe the case of a 35-year-old woman in remission from UC who presented with frequent diarrhea and abdominal pain. She was treated with ciprofloxacin for infectious enterocolitis at a local hospital; however, her symptoms did not improve. A colonoscopy revealed yellow-white plaques with edematous, erythematous from the proximal ascending colon to the cecum, and feces positive for C. difficile toxin. She was treated with metronidazole (500 mg, three times a day) for two weeks, and improved rapidly. Physicians should carefully examine the entire colon via colonoscopy, and perform stool exams for C. difficile in patients with UC who have been treated with antibiotics and in those who develop prolonged diarrhea despite medical treatment.