The clinical findings and laboratory results from 18 patients with clear-cut transient global amnesia (TGA) were compared with the results from 90 nonischemic neurological control patients using case-control analysis. A prior episode of cerebral ischemia, generally in the posterior circulation, was the most significant risk factor for TGA. Other risk factors for cerebrovascular disease were more prominent in the TGA group, but this association became less significant when cerebral ischemia was controlled for. Migraine, epilepsy, and psychiatric disorders were not significantly associated with TGA. In 5 of 13 patients, computed tomography showed focal thalamic and temporal lobe abnormalities. The recurrence rate was 7.0% for both TGA and subsequent cerebral ischemia. We conclude that TGA is closely linked to cerebrovascular disease. Further, prior damage to anatomical structures critical to memory may be necessary for the expression of this syndrome.