Background: While vaccines have reduced the incidence of vaccine-preventable diseases, vaccine hesitancy threatens the re-emergence of childhood infectious diseases. Purpose: This randomized controlled study evaluated an online vaccine education program to advance vaccine acceptance among middle-school students. Methodology: Study participants were randomly assigned to an intervention group who viewed the VEP videos or to a comparison group who viewed a science-based video unrelated to vaccines. Results: Knowledge scores improved in both groups and more favorable shifts in vaccine-related beliefs and attitudes occurred in the intervention than in the comparison group. Conclusions: This program can be feasibly delivered via an online platform to middle school students, resulting in shifts in vaccine-related knowledge, beliefs and attitudes. Implications: Delivering evidence-based content to instruct about vaccine effectiveness and safety is an area in which school nurses have demonstrated an important role as a resource for patient education to promote vaccine advocacy.