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Background: Vaccination rates for measles, mumps, and rubella (MMR) and diphtheria, tetanus, pertussis, and polio (Tdap-IPV) are not optimal among German adolescents. Education in combination with easy access to vaccination may be a promising approach to improve vaccination rates. The present paper describes a pilot study of a planned cluster randomized controlled trial (cRCT) in which we aim to improve MMR and Tdap-IPV vaccination rates together with knowledge and self-efficacy in a school setting.Methods: The study covered 863 students from 41 classes of four schools. The optimization and feasibility of access to schools, recruitment strategies, intervention, and assessment procedures were examined. The course and content of the educational unit were evaluated with a mixed-methods approach. A pre-post measurement design was tested for the vaccination rate in all schools. Additionally, at two schools, improvement in vaccination-related knowledge and perceived self-efficacy were measured by questionnaire pre-educational unit (n=287) and post-educational unit (n=293). The remaining two schools provided only postintervention data. Finally, we evaluated the psychometric properties (i.e., reliability, retest reliability, and change rates) of the questionnaire, applying Cronbach's alpha, factor analyses, generalized estimating equations and linear mixed models.Results: The findings of the pilot study indicated good feasibility. Of the total sample, 437 students (50.9%) brought their vaccination cards to school, 68 students received Tdap-IPV vaccinations, and 11 received MMR vaccinations. Out of six knowledge questions, on average, the students had M=2.84 (95% CI [2.69, 3.10]) correct answers before and M=4.45 (95% CI [4.26, 4.64]) after the class. Ranging from 1 to 4, the self-efficacy scale changed by 0.3 points (p <.001); Cronbach's alpha was 0.67 and 0.76 pre- and post-educational unit, respectively, and a one-factor solution was found. Content analysis of the five semistructured group interviews (n=12, 58.3% female) showed that all students found the length of the intervention to be appropriate. The teaching methods, including interactive and social media components, were perceived as very good.Conclusions: A school-based educational and on-site vaccination intervention appears to be feasible in terms of procedures and the adequacy of the instruments for the adolescent target group.Trial Registration: ISRCTN, ISRCTN18026662 . Pilot study for main trial registered 8 December 2017. [ABSTRACT FROM AUTHOR]