Ischemic brain injury (stroke) is a major cause of status epilepticus (SE). In our database of 529 adult SE cases, acute or remote cerebrovascular accidents (CVA) were a primary cause of SE for 41% of the patients overall and for 61% of the elderly patients. SE in the setting of acute CVA has a very high mortality, approaching 35%. The degree to which mortality can be attributed to the severity of the underlying CVA etiology vs. the effect of SE has not been evaluated. To address this issue, we prospectively studied patients with SE and acute CVA and compared them to control populations with acute CVA alone or with SE and remote CVA. The groups did not significantly differ with regard to age, sex, or radiographic lesion size. Mortality was unrelated to lesion size in the CVA and SE group. Overall, acute CVA and SE patients had an almost three-fold increase in mortality compared to the CVA group and an eight-fold increase compared to the SE and the non acute (remote) CVA group. Logistic regression analysis demonstrated a statistically significant synergistic effect of SE and CVA on mortality. This is the first study to document that the high mortality of SE and acute CVA is not solely due to the severity of the underlying CVA etiology, but due to the synergistic effect of combined injuries from SE and cerebral vascular ischemia.