To determine the specific high-risk characteristics and temporal window associated with Diphtheria, Tetanus, and acellular Pertussis (DTaP) vaccine-precipitated infantile epileptic spasms syndrome (IESS), providing evidence for optimizing vaccination safety strategies, we conducted a multicenter retrospective cohort study of 564 patients with long-term follow-up (6.5-10.5 y). Patients were stratified by seizure onset interval into Vaccination-proximate (≤72 hours) and distant (>72 hours) groups. The proximate group (n = 53, 9.4%) exhibited a significantly younger age distribution (median [IQR]: 5.0 [3.0-6.0] vs. 5.0 [4.0-7.0] months, p = .04) and higher DTaP exposure (71.7% vs. 51.3%). Multivariable logistic regression in an etiologically analytic cohort (n = 541) identified the DTaP primary series as a significant independent precipitant for rapid onset (Dose 1: OR = 4.00; Doses 2 & 3: OR = 4.67) compared to other inactivated vaccines. Crucially, no increased risk was observed for the DTaP booster (Dose 4) or non-DTaP inactivated vaccines. Kaplan-Meier analysis confirmed a steep rise in seizure incidence within 72 hours post-primary DTaP. Long-term follow-up revealed no significant differences in all-cause mortality, seizure remission, or educational placement (p > .05) between groups, indicating that vaccination merely precipitated disease onset without altering the etiology-determined prognosis. This study, based on the full-course observation of school-aged children, is the first to validate the specificity of the DTaP-IESS association. The DTaP primary series is a critical precipitating factor for rapid onset (≤72 hours) in infants with underlying epileptogenic susceptibility. We recommend a stratified immunization strategy for high-risk infants: adhering to schedules for non-DTaP vaccines while adopting a prudent "delay-but-not-refuse" approach for DTaP to balance neurological safety with herd immunity.