Summary Purpose:  Cases of severe childhood epilepsies in temporal association with vaccination have great impact on the acceptance of vaccination programs by parents and health care providers. However, little is known about the type and frequency of seizures and epilepsy syndromes following vaccination. This study aims to describe the clinical features of children presenting with seizures after vaccination using a register‐based cohort. Methods:  We surveyed the national German database of adverse events following immunization (AEFI) for reported seizures and epilepsies in children aged 0–6 years. All cases reported in 2006–2008 were analyzed retrospectively; available clinical information was reevaluated and classified by seizure type and epilepsy syndrome. Key Findings:  In total, 328 cases reported between 2006 and 2008 were included. Data supportive of seizures or epilepsy were present in 247 (75.3%) of 328 patients with a mean interval between the vaccination and the epileptic event of 24 h and 7.5 days for inactivated and attenuated vaccines, respectively. Fifty‐one (15.5%) of 328 patients presented with syncope, hypotonic–hyporesponsive episodes, or other nonepileptic events. Information was insufficient for classification into epileptic versus nonepileptic events in 30 (11.3%) of 328 patients. For cases with confirmed seizures, febrile seizures were present in 121 (49%) of 247 cases, and 38 (15.4%) of 247 patients had single afebrile seizures. Status epilepticus was described in 21 (8.5%) of 247 patients. Thirty‐one (12.6%) of 247 patients presented with various pediatric epilepsy syndromes. Severe childhood epilepsies (Dravet syndrome, West syndrome, Lennox–Gastaut syndrome, or Doose syndrome) were diagnosed in 29 (11.7%) of 247 patients, with the vaccination‐associated event being the first documented seizure in 15 (51.7%) of 29 patients. Significance:  Vaccination‐associated seizures present in the setting of various epilepsy syndromes, including severe childhood epilepsies in >10% of cases. Early diagnosis of the corresponding epilepsy syndromes and confirmation of an underlying etiology is important for treatment decisions, genetic counseling, and public health evaluation of vaccine safety.

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