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Acute otitis media (AOM) nonresponsive to antibiotics is most commonly caused by antibiotic-resistant Streptococcus pneumoniae and Haemophilus influenzae. A strategy for treating these infections with parenteral ceftriaxone was adopted at the Children’s Hospital Iceland. The 10-valent pneumococcal H. influenzae protein D-conjugate vaccine was introduced into the vaccination program in Iceland in 2011. The aim was to study its effect on the incidence of AOM with treatment failure.This retrospective observational study included children who visited the Children’s Hospital Iceland because of AOM or received ceftriaxone, regardless of indication from 2008–2015. Incidence rate was calculated for prevaccine (2008–2011) and postvaccine (2012–2015) periods using person-years at risk within the hospital’s referral region. Incidence rate ratio of ceftriaxone treatment episodes of AOM was calculated using the Mantel–Haenzel method adjusting for age. Incidence risk ratio of ceftriaxone treatment if presenting to the hospital with AOM was calculated to adjust for rate of AOM visits.Visits for AOM decreased from 47.5 to 33.9 visits per 1000 person-years, incidence rate ratio (IRR) 0.86 (95% confidence interval [CI]: 0.81–0.91), P < 0.001. Fewer AOM episodes were treated with ceftriaxone, decreasing from 6.49 to 2.96 treatment episodes per 1000 person-years, with an overall Mantel–Haenzel adjusted IRR 0.45 (95% CI: 0.37–0.54; P < 0.001). This remained significant after adjusting for the decrease in AOM visits, IRR 0.53 (95% CI: 0.44–0.63; P < 0.001).Visits for AOM and ceftriaxone use decreased significantly after H. influenzae protein D-conjugate vaccine introduction. The observed decrease in ceftriaxone use is presumed to represent a decline in AOM with treatment failure, secondary to a decrease in resistant infections.