Background: Febrile seizures are VAERS often associated with whole-cells Diphtheria-Pertussis-Tetanus vaccines. Aim: To analyze the association of febrile seizures with the administration of pentavalent vaccine in children under two-years-old assisted in the Centro Hospitalario Pereira Rossell (CHPR), in Montevideo during 2014. Methods: Self-controlled case series study. We included children from Montevideo from two to 24-month-old at the time of admission, with diagnosis of febrile seizure at the time of discharge. We estimated the relative risk in three time periods: 0 to 3 days (risk period), 4 to 14 days (wash-out) and more than 14 days after vaccination (no-risk). Results: We recorded 135 febrile seizures in 114 children, 16 of whom presented two or more events. The total number of events was 7 (5.2%) in risk periods and 8 (5.9%) in wash-out periods. The risk period showed a significantly increased risk (RR = 4.14, CI 95% = [1.73; 8.36]). Conclusions: This work allowed us to establish a national base line for the risk of febrile seizures associated with pentavalent vaccination, by using for the first time in the country a methodology specifically designed for this goal.