Extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest is increasing in usage, but risk factors for seizures are largely unknown. We included adult ECPR patients in the Extracorporeal Life Support Organization Registry from 512 extracorporeal membrane oxygenation (ECMO) centers (2013–2023). Seizures were determined clinically or by electroencephalogram. Acute brain injury included ischemic stroke, hypoxic-ischemic brain injury, and intracranial hemorrhage. Among 13,783 ECPR patients (median age = 56.7 years, 69% = male), 346 (3%) experienced seizures. Of these, 204 (59%) were clinically detected, 193 (56%) were electroencephalogram (EEG)-detected, and 51 (15%) were detected by both. From 2013 to 2023, ECPR cases increased (n = 442 to 1,123; p < 0.001) while seizure incidence declined (5–3%; p = 0.02). Mortality was higher among patients with seizures (77% vs. 69%; p < 0.001). Patients with seizures died earlier (7.3 days) than patients without 15 seizures (10.8 days, p < 0.0001). In multivariable logistic regression, ABI (adjusted odds ratio [aOR] = 2.65, 95% confidence interval [CI] = 1.89–3.67), moderate hyperoxia (aOR = 1.60, 95% CI = 1.05–2.39), arrhythmia (aOR = 1.44, 95% CI = 1.00–2.03), and partial pressure of carbon dioxide (ΔPaCO₂) (aOR = 1.12, 95% CI = 1.06–1.17) were significant risk factors for seizures. In multivariable logistic regression, after adjusting for ABI, seizures (aOR = 2.32, 95% CI = 1.09–4.95) increased the risjk of 90 day mortality. Extracorporeal cardiopulmonary resuscitation use increased from 2013 to 2023, with decreasing incidence of seizures, although this trend may be influenced by underreporting and evolving EEG practices. Seizures were an independent risk factor for 90 day mortality.