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Concerns regarding vaccine safety are increasing along with lack of compliance to vaccination schedules. This study aimed to assess vaccination-related risks and the impact of a Special Immunization Service (SIS) at the Pediatric Emergency Department (PED) of Padua on vaccination compliance among participants.This retrospective cohort study included all children attending the SIS from January 1st 2002 to December 31st 2015. The Service is divided into a clinic (SIS-C) where all referred children undergo a pre-vaccination visit and an area within the Pediatric Emergency Department (SIS-PED) where children are vaccinated if indicated. During each SIS-C visit, age, gender, admission criteria and scheduled vaccinations were recorded, with any vaccine-related adverse events captured during SIS-PED visits. Follow-up was conducted to evaluate vaccination plan completion.359 children received 560 vaccine administrations (41.3% MMR/MMRV, 17.5% hexavalent) at the SIS during the 14 year study. Admission criteria were adverse events after previous vaccination (immediate, IgE/not IgE mediated, and late) in 27.2% of cases, non-anaphylactic allergies (mostly egg allergy) in 42.7% and anaphylaxis in 10.3%. After vaccination, 15/560 (2.7%) mild adverse events were observed. 96.3% of children vaccinated at least once at the SIS-PED and available for follow-up completed their vaccination plan, in contrast to 55.5% of children referred to the SIS-C who were not vaccinated in SIS-PED.For children referred to SIS-C and available for follow-up, vaccination in SIS-PED was associated with more frequent completion of vaccination plans, indicating a benefit of the service to vaccine coverage. The low number and mild severity of adverse events reported after vaccination of high-risk children in SIS-PED attest to the safety of the service.