OBJECTIVES: Receipt of diphtheria-tetanus-whole-cell pertussis vaccine (diphtheria-tetanus toxoids-pertussis [DTP]) is associated with seizures. Limited population-based studies have been conducted on the risk for seizures after receipt of diphtheria-tetanus-acellular pertussis vaccine (diphtheria-tetanus-acellular pertussis [DTaP]). METHODS: We conducted a retrospective study from 1997-2006 by using risk-interval cohort and self-controlled case series (SCCS) analyses on automated data at 7 managed care organizations that participate in the Vaccine Safety Datalink (VSD). Eligible children included the 1997-2006 VSD cohort of patients who were aged 6 weeks to 23 months and had not received DTP during the study period. A seizure event (febrile or afebrile) was defined by International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses assigned to an inpatient or emergency department setting. The exposed period was composed of a predefined 4 person-days after each DTaP dose. All of the remaining observation periods outside the exposed periods were categorized as unexposed. The risk-interval cohort method compared the incidence of seizures between the exposed and unexposed cohorts. In the SCCS method, the comparison was performed between the same patient’s exposed and unexposed period. RESULTS: We identified 7191 seizure events among 433,654 children. The adjusted incidence rate ratio of seizures across all doses was 0.87 in cohort analysis and 0.91 in SCCS analysis. CONCLUSIONS: We did not observe an increased risk for seizures after DTaP vaccination among children who were aged 6 weeks to 23 months. These findings provide reassuring evidence on the safety of DTaP with respect to seizures.