Background: Status epilepticus (SE) frequently does not respond to common first-line anticonvulsants. In a substantial portion of patients, administration of anticonvulsant anesthetics is inevitable. Even this aggressive approach fails to terminate SE in an undefined number of cases. We have coined the term malignant SE for this most severe variant of SE. Objective: To assess frequency, risk factors, and in-hospital outcome of malignant SE. Design: Retrospective cohort study. Setting: Neurologic intensive care unit of a large university hospital. Patients: Sample of 35 episodes of SE not responding to firstline anticonvulsants in 34 patients. Main Outcome Measures: Predictive and prognostic features of episodes of malignant SE with persistent epileptic activity after high-dose anesthetics compared with features of the remainder of cases wi th refractory SE and persistent epileptic activity after failure of first-line anticonvulsants. Results: Status epilepticus that could not be controlled by fir st-line anticonvulsants resulted in malignant SE in 20%of cases. Patients with malignant SE were significantly younger than patients with refractory SE (P=.03 ). Encephalitis was identified as an independent risk factor for malignant SE (P =.008). Outcome in malignant SE was poor, with significantly longer duration of seizure activity (P < .001), longer stay in the neurologic intensive care unit ( P < .001) and in the hospital (P=.007), and more patients with functional depend ency at discharge from the hospital (P=.04). Conclusions: Malignant SE is not ra re after failure of first-line anticonvulsants. The patient at risk is typicall y young and suffers from encephalitis. Such patients should be treated aggressiv ely early in the course of SE to prevent malignant SE. Background: Status epilepticus (SE) frequently does not respond to common first-line anticonvulsants. In a substantial portion of patients, administration of anticonvulsant anesthetics is inevitable. Even this aggressive approach fails to terminate SE in an undefined number of cases. We have coined Objective: To assess frequency, risk factors, and in-hospital outcome of malignant SE. Design: Retrospective cohort study. Setting: Neurologic intensive care unit of a large university hospital. Patients: Sample of 35 episodes of SE not responding to first line anticonvulsants in 34 patients. Main Outcome Measures: Predictive and prognostic features of episodes of malignant SE with persistent epileptic activity after high-dose anesthetics compared with features of the remainder of cases wi th refractory SE and persistent epileptic activity after failure of first-line anticonvulsants. Results: Status epilepticus that could not be contro lled by fir st-line anticonvulsants resulted in malignant SE in 20% of cases. Patients with malignant SE were significantly younger than patients with refractory SE (P = .03). Encephalitis was identified as an independent risk factor for malignant SE (P = .008). Outcome in malignant SE was poor, with significant longer duration of seizure activity (P <.001), longer stay in the neurologic intensive care unit (P <.001) and in the hospital (P = .007), and more patients with functional dependancy at discharge from the hospital (P = .04). Conclusions: Malignant SE is not ra re after failure of first-line anticonvulsants. The patient at risk is typicall y young and suffers from encephalitis. Such patients should be treated aggressiv ely early in the course of SE to prevent malignant SE.