Many students are afraid of receiving vaccinations at school. We implemented a novel, multifaceted knowledge translation intervention incorporating evidence-based vaccination coping strategies-The CARD™ System (C-Comfort, A-Ask, R-Relax, D-Distract)-and evaluated impact on student attitudes, knowledge, coping strategies used, and symptoms during school-based vaccinations. Mixed methods. Ten schools participated in a controlled clinical trial: five experimental and five control. Experimental School (ES) students completed a knowledge and attitudes survey during an in-class CARD™ educational session prior to school vaccinations and selected coping strategies for upcoming vaccinations. Control School (CS) students received the usual vaccine education lesson, which did not include information about or selection of coping strategies. At all schools and during both vaccination clinic visits (fall and spring), injecting nurses recorded specific coping strategies used, and students independently rated their fear, pain, and dizziness during vaccinations. Focus groups were conducted at five schools after all clinics were completed (three ES, two CS). ES students had higher knowledge (P<0.001), less fear (P=0.03), and greater willingness to be vaccinated (P=0.001) after the in-class education session. Students rated the education as understandable, sufficient, useful, and that it prepared them for vaccinations. During school vaccination clinics, ES students selected more coping interventions than CS students. There were fewer students with high levels of fear (P=0.008) and dizziness (P=0.04) in the ES group. In round 2, fewer students (P=0.02) in the ES group returned to the clinic postvaccination because they were feeling unwell. ES students participating in focus groups scored higher on their knowledge test (P<0.001) compared with CS students and reported learning and benefitting from CARD™. This small-scale implementation study provides preliminary evidence of the effectiveness of CARD™ in improving vaccination experiences for students at school. Future research is recommended that examines CARD™ in different settings to confirm these results.