Introduction: Patients with intracerebral cavernous malformations (ICMs) may present with or later develop seizures. There are limited data regarding the clinical demographics of these patients, predictors of medically treatable versus medically refractory seizures, and long term seizure outcome. Objective: We aimed to characterize the clinical and radiographic features of supratentorial ICMs that present with seizures and describe their response to medical treatment. Methods: Patients with supratentorial ICMs were identified from a radiographic database for cases seen between 1989 and 1999. Clinical and radiographic information was abstracted and prospective follow up was obtained. Medically refractory seizures were defined as patients who were not seizure-free at last follow up, or who underwent surgery for refractory seizures. Results: A total of 206 patients were identified with a radiographic diagnosis of supratentorial ICM, 103 (50%) of whom presented with seizures and 7 (3%) who later developed seizures. Compared to those with seizures, patients without seizures were more likely to have a subcortical supratentorial ICM and to be on an antithrombotic agent. Intracerebral hemorrhage (ICH) at diagnosis did not predict presentation with seizure at diagnosis. Among the 59 patients treated with antiepileptics only, 16 (27%) were seizure-free at last follow up, 7 of whom no longer required medication and 8 of whom were controlled on a single agent. In the remainder of patients who were not seizure-free, seizure frequency was reduced in 37%, unchanged in 12%, increased in 5%, and unknown in 19%. Of the total 110 patients with seizures, 46 (42%) underwent at least one surgical removal of an ICM for medically refractory seizures. Conclusions: To date this study is one of the largest cohorts of ICM patients with seizures. Seizure is a common presentation in patients with cortical supratentorial ICMs. The presence of ICH at ICM diagnosis is not related to an increased occurrence of seizures at presentation. One-fourth of patients treated with antiepileptics alone eventually become seizure-free, almost half of which do not require medication at follow-up, suggesting that some non-surgical patients may not require life-long antiepileptic therapy.