Intramural dissecting hematoma is an unusual esophageal condition with a threatening presentation but excellent prognosis when managed conservatively. We report the case of an 88-year-old woman who developed an intramural hematoma of the esophagus after intravenous thrombolysis for an acute ischemic stroke. Before thrombolysis, nasogastric intubation was attempted unsuccessfully. She was kept on nil by mouth, intravenous hydration, proton pump inhibitor, antiemetics, and an antibiotic initiated 2 days before for periodontal disease. The esophageal hematoma regressed, and she resumed oral diet asymptomatically. To our knowledge, this is the first report of this type of lesion after thrombolysis for an ischemic stroke. A brief discussion and literature review are presented.