Purpose: To identify the probable etiologies and characteristics of new-onset seizures after orthotopic liver transplantation (OLT) and to assess their clinical implications and prognosis. Methods: We retrospectively analyzed the clinical, electrophysiologic and laboratory data of 17 patients with new-onset seizures after OLT among 367 adult and pediatric patients who underwent OLT between 1999 and 2001. Results: A suspected etiology of seizures was identified in most patients, including 6 (35.2%) with neurotoxicity due to immunosuppressive therapy, 4 (23.5%) with cerebrovascular disease, 3 (17.6%) with severe metabolic derangement by sepsis or rejection, and 1 each (5.8%) with hyperglycemia and brain edema due to fulminant hepatic failure. Causative factors could not be identified in 2 patients (11.8%). Seizures recurred in 15 patients (88.2%), with 9 occurring on the same day as the original seizure. Attacks caused by neurotoxicity tended to have an earlier onset, within 1 week in 4 of 6 patients, than those caused by cerebrovascular disease and sepsis/rejection, but this was not statistically significant. A total of 21 EEGs were performed in 13 patients. Eleven patients had abnormal EEG findings, of whom 4 (30.7%) showed epileptiform discharges, but the outcome of patients with epileptiform activity did not differ statistically from that of patients without such discharges (p > 0.6). The incidence of poor outcome (death or persistent vegetative state) in the group with seizures was almost 10 times higher than in the group without seizures (52.9 vs. 5.7%, p < 0.001). The prognosis of patients with seizures due to cerebrovascular disease and severe metabolic derangement by sepsis/rejection was poorer than that of patients with seizures caused by the neurotoxicity of immunosuppressive drugs (p < 0.02), suggesting that the underlying cause of seizures is important in determining prognosis. Of 8 patients who survived, 1 was lost to follow-up. The long-term outcome of seizures in surviving patients was excellent, with all survivors available for follow-up being seizure-free for a mean follow-up of 42.5 months (range, 16–58 months). Conclusion: New-onset seizures after OLT may herald fatal outcome, especially in patients with cerebrovascular disease or sepsis. The prognosis of seizures in survivors is excellent, and long-term antiepileptic drugs are not required in most cases.