We have seen two cases of a segmental ischemic colitis develop during nonsteroidal antiinflammatory drug (NSAID) treatment. No other possible etiologic factors were shown. The short-term clinical course and the follow-up were uneventful. NSAIDs have been reported to cause different lesions in the large bowel, either by worsening preexisting colonic diseases or by inducing a primary pathology. We suggest that ischemia should be considered a possible mechanism of NSAID-associated colitis. Such ischemic colitis, not triggered by severe cardiovascular disease or operation, may be related to NSAIDs more often than currently recognized.