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Streptococcus pneumoniae is the leading cause of acute otitis media (AOM). Ten-valent pneumococcal conjugated vaccine (PCV-10) was introduced to the Chilean National Immunization Program (NIP) in 2011. The aim of this study was to estimate the frequency of AOM in children <24 months of age attending the emergency department (ED) of Hospital Sótero del Río (HSR) 4 years before and 4 years after the introduction of PCV-10 in the Chilean NIP.Register-based nested case-control study. Cases (n = 1907) were all children <24 months of age with a clinical diagnosis discharge of AOM at the ED of HSR, and controls (n = 244,334) were all other children <24 months of age attended at the same ED in the same time period, with any other discharge diagnosis. The data were obtained through HSR Statistical Service.In the study period, there was a mean of 30,695 children <24 months managed each year at the ED of HSR. The percentage with AOM in the prevaccine period was 0.94% and in the postvaccine period was 0.62%, respectively (P = 0.026). Exposure to the PCV-10 was associated with a decreased risk to develop AOM in children <24 months, with an odds ratio of 0.659 (95% confidence interval: 0.60–0.72).Our study showed a significant decrease in the percentage and risk of AOM in children <24 months of age who visited the ED of HSR after implementation of PCV-10 in the NIP in Chile.