A Clostridioides difficile infection (CDI) is one of the major nosocomial diarrheal diseases. Pseudomembranous colitis (PMC) is a characteristic endoscopic finding of CDI, manifested by white or yellowish plaque covering the colonic mucosa. Ischemic colitis is inflammation of the colon manifested by mucosal denudation and friability. Ischemic colitis is rarely associated with CDI. The treatment response might be delayed when CDI is complicated with other diseases that cause diarrhea. Thus far, reports of CDI concomitant with Cytomegalovirus (CMV) colitis are rare. This paper reports a case of PMC and ischemic colitis associated with CDI and CMV infection. After two weeks of oral vancomycin and intravenous metronidazole, the patient’s diarrhea was not improved. Follow-up sigmoidoscopy was performed, and a CMV infection was identified at areas of broad ulceration where ischemic colitis occurred. Finally, the patient was cured with ganciclovir. Follow-up sigmoidoscopy showed an improvement in ischemic colitis. (Korean J Gastroenterol 2023;81:133-136)