We present two cases of indomethacin-induced perforation of the distal small intestine. Both patients were male and undergoing oral indomethacin therapy. Both presented acute abdomen with diffuse peritonitis secondary to perforations located in the antimesenteric border of the terminal ileum. Histopathological lesions of the intestinal wall showed transmural infiltration, congestion, and hemorrhage; their severity was related to higher doses and longer duration of indomethacin therapy.