Objective: To identify risk factors associated with acute otitis media treatment failure (AOMTF) among 13-valent pneumococcal conjugate vaccine (PCV) immunized children. Methods: In this retrospective study, we identified children < 12 years who were admitted to our hospital November 2017-October 2020. Children were categorized either as acute otitis media treatment failure (AOMTF), if they received adequate pre-admission antibiotics, or as AOM without treatment failure (AOMwTF), if they did not receive any pre-admission antibiotics. We collected demographics, clinical behavior, laboratory results, length and hospitalization course. Hospitalization was justified if previously treated properly. Results: The AOMTF group included 84 children (43 boys, mean age: 1.30 +/- 0.83 years), whereas the AOMwTF group included 251 children (132 boys, mean age: 1.20 +/- 0.89 years). AOMTF accounted for 25% of all AOM admissions. Among the AOMTF group, 46 (54.8%) were treated with amoxicillin and 24 (28.6%) with amoxicillin/clavulanic acid. Risk factors for AOMTF included recurrent AOM episodes history (30.9% vs 5.5%, OR 7.6, 95%CI 3.5-15.4, p < 0.001), otorrhea (29.4% vs 9.5%, OR 4, 95%CI 2.1-7.5, p < 0.001), tympanic membrane perforation (14.2% vs 4.3%, OR 3.6, 95%CI 1.5-8.6, p < 0.0019). Children with AOMTF were treated more with 2nd-or 3rd-line antibiotics (90.2% vs 65.9%, OR 4, 95%CI 2.2-10.4, p < 0.001), and underwent more myringotomy/ventilation tube insertions (14.4% vs 6.9%, OR 2.3, 95%CI 1.0-5.0, p = 0.037). Mean admission durations were similar: 3.83 +/- 1.6 days in the AOMTF group vs 3.37 +/- 2.77 days in the AOMwTF group (p = 0.15). Conclusion: Risk factors associated with AOMTF should be identified early during the AOM course to reduce complication rates and surgery referral.