Two adult cats from the same household developed acute diarrhea. Clostridium difficile toxins were detected in the feces of both cats, whereas other recognized causes of diarrhea were not identified. Supportive medical treatment and metronidazole were administered and both cats responded well. A fecal sample obtained from 1 of the affected cats after treatment and a fecal sample obtained from a clinically normal cat in the household did not contain C difficile toxins. The role of C difficile in enteric disease in cats has not been extensively studied and is unclear; however, our findings suggest that toxigenic strains of C difficile may cause diarrhea in cats.