Background:We aimed to elucidate variables associated with coronavirus disease 2019 (COVID-19) vaccine compliance in adolescents and devise targeted interventions. Our secondary aim was to compare the rates of severe acute respiratory syndrome coronavirus 2 infection, hospitalizations and deaths between vaccinated and unvaccinated adolescents.Methods:A retrospective review of electronic medical records was performed on all adolescents 12–17 years of age registered at Clalit Health District in Israel during January 1, 2021, to November 18, 2021, with characterization by vaccination status against COVID-19. Univariate and multivariable analyses were employed to identify predictors of vaccination.Results:Of the 43,919 subjects included in the study, 28,207 (64.2%) were vaccinated. Non–ultraorthodox Jewish adolescents had a higher vaccination rate than the minorities Arabs or ultraorthodox Jews (72.5%, 66.2% and 40.5%, respectively, P < 0.001). Adolescents of high socioeconomic status had nearly 2-fold higher vaccination rates than those of low socioeconomic status (80.4% vs 42.3%; P < 0.0001). Adolescents 16–17 years old had a higher rate of COVID-19 vaccination than those 12–15 years old (72.5% vs 60.6%, P < 0.001), as were girls versus boys (64.7% vs 63.8%, P = 0.047). Multivariate analysis identified 3 independent variables that were significantly (P < 0.001) associated with low vaccination: ultraorthodox sector, Arab population, and underlying obesity (hazard rations 0.42, 0.72 and 0.84, respectively). Vaccination was significantly associated with reduced severe acute respiratory syndrome coronavirus 2 infection, hospitalization and death (P < 0.001).Conclusion:This study highlights several pediatric populations with low COVID-19 vaccine compliance. Targeted interventions aimed at these populations are suggested with consideration of their special cultural, social and societal characteristics.