School-based immunizations are fear-inducing events for many students. We developed an immunization delivery framework called the CARD™ (Comfort, Ask, Relax, Distract) system that incorporates interventions from an evidence-based clinical practice guideline to reduce immunization stress-related responses, including fear. In this large, pragmatic cluster randomized trial, CARD™ was evaluated for immunizations in grade 6 and 9 students in Calgary, Canada.  CARD™ reduced student fear and is recommended to improve the safety of vaccine administration and experiences of students undergoing school immunizations. Improving immunization delivery has the potential to promote positive attitudes about immunization and vaccine acceptance in the future.