There are numerous literature reports of oral contraceptive-induced (estrogen and progesterone) ischemic bowel disease. However, Premarin-induced (equine conjugated estrogen) intestinal ischemia has rarely been reported. We describe three cases of Premarin-induced ischemic colitis. In contrast to oral contraceptive-induced ischemic colitis, Premarin-induced ischemia is restricted to the colon, has not required surgical therapy, can have a chronic or chronic intermittent course, may be reversible despite continued usage of Premarin, and may present with nonspecific abdominal and colonic symptoms.