Objective:We aimed to report the pattern of usage and efficacy of antiepileptic drugs (AEDs) in patients with autoimmune epilepsy (AE).Methods:We retrospectively studied the Mayo Clinic's electronic medical record of patients with AE in which seizures were the main presenting feature. Clinical data, including demographics, seizure characteristics, type of AED and immunotherapy used, presence of neural antibody, and treatment outcomes, were reviewed.Results:The medical records of 252 adult patients diagnosed with autoimmune encephalitis and paraneoplastic disorders were reviewed. Seizure was the initial presentation in 50 patients (20%). Serum and/or CSF autoantibodies were detected in 41 (82%) patients, and 38 (76%) patients had neural autoantibodies. The majority (n = 43, 86%) received at least 1 form of immunotherapy in combination with AEDs, while the remainder received AEDs alone. Twenty-seven patients (54%) became seizure free: 18 (36%) with immunotherapy, 5 (10%) with AEDs alone, and 4 (8%) with AEDs after immunotherapy failure. Levetiracetam was the most commonly used (42/50); however, it was associated with 0% seizure-free response. AED seizure-free responses occurred with carbamazepine (n = 3) [3/16, 18.8%], lacosamide (n = 3) [3/18, 16.6%] with phenytoin (n = 1) [1/8, 12.5%], or oxcarbazepine (n = 2) [2/11, 18.1%]. Regardless of the type of therapy, voltage-gated potassium channel-complex antibody–positive patients were more likely to become seizure free compared with glutamic acid decarboxylase 65 antibody–positive cases (12/17 vs 2/10, p = 0.0183).Conclusions:In select patients, AEDs alone were effective in controlling seizures. AEDs with sodium channel blocking properties resulted in seizure freedom in a few cases. Prospective studies are needed to clarify AED selection and to elucidate their immunomodulatory properties in AE.