0157:H7 is a known etiologic agent of hemorrhagic colitis. The clinical and histologic picture of colitis is largely similar to that of ischemic colitis, with areas of submucosal hemorrhage and edema, erosions, and ulcerations. We present a case report and review of the literature. A 52-year-old HIV-positive man, in apparently good immunologic condition, developed severe hemorrhagic colitis characterized by the onset of multiple colonic perforations and an unfavorable outcome. The diagnosis of 0157:H7 colitis should therefore be considered in all patients with indeterminate hematic diarrhea. Further studies are warranted to verify whether HIV infection may play a determinant role in the clinical course of 0157:H7 infection.