Hyperacute, spontaneous, and severe parenchymal postischemic hemorrhage is considered rare but might be frequently misdiagnosed as primary intracerebral hemorrhage. The authors report 2 patients with catastrophic postischemic hemorrhage unrelated to anticoagulation, thrombolytics, or coagulopathy. Patient 1 was a 73-year-old woman with left posterior frontal lobe infarction, followed at 5.5 hours by massive postischemic hemorrhage leading to death. Patient 2 was a 52-year-old man with recent brain irradiation who developed left middle cerebral artery occlusion and basal ganglia infarction. Initial gradient-echo magnetic resonance imaging (MRI) showed petechial hemorrhage within areas of infarction and widespread old microbleeds. He developed massive postischemic hemorrhage at 12 hours, leading to death. The authors conclude that early brain imaging is essential to distinguish postischemic from primary brain hemorrhage. In patients with ischemic stroke, MRI findings such as hyperacute petechial hemorrhage or chronic cerebral microbleeds might predict subsequent parenchymal hemorrhage and thus have implications for tissue plasminogen activator use.