Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a variety of gastrointestinal side effects. Effects on the large intestine have been reported with increasing frequency. Recognition of NSAID-induced colonic lesions has been confounded by variable clinical presentations, variable pathologic findings, and unfamiliarity of this entity among clinicians. We have recently seen three cases of NSAID-induced cecal ulcerations in patients undergoing right colectomy. A correct preoperative diagnosis was not made in our patients, one of whom presented with an acute abdomen and two in whom there was an inability to rule out carcinoma. The gross, radiographic, and histologic findings in each case consisted of a characteristic transverse ulceration with thin diaphragm-like scarring. NSAID-induced cecal ulcers can have a variety of presentations to the general surgeon, are likely to be misdiagnosed preoperatively, but may be recognized based on characteristic gross features evident by radiography and colonoscopy, along with a careful history. Review of recent literature suggests that laparotomy can be avoided when diagnosis is considered, but operation is indicated for complications, such as hemorrhage, obstruction, or perforation, and when carcinoma cannot be adequately excluded.