Rationale and Objectives: Severe reactions to radiographic contrast agents can be life threatening, and although they are rare, effective recognition and management are essential to improving outcomes. A high-fidelity radiology simulation course for radiology residents and technologists focusing on severe contrast reactions and immediate treatments was designed to test the hypothesis that knowledge would improve with this educational intervention. Materials and Methods: A prospective pretest and posttest study design was used. Residents and technologists worked in teams of three to five members. Learning objectives focused on demonstrating when and how to use basic life support skills and epinephrine auto-injectors. Each resident and technologist was administered a pretest prior to the start of the case scenarios and a posttest following the debriefing session. Scores from the pretest and posttest for the residents and technologists were compared using a paired-samples t test. Results: Nineteen radiology residents and 11 radiology technologists participated. The average test scores were higher and improved significantly following the simulation experience for both the radiology residents (57% vs 82%, P < .001) and technologists (47% vs 72%, P = .006). Anonymous evaluations demonstrated that the experience was well received by residents and technologists, with 97% of learners (29 of 30) rating the experience as extremely or very helpful. Important learning themes included the knowledge of epinephrine auto-injector use and basic life support skills. Discussion: High-fidelity simulation for radiology residents and technologists focusing on epinephrine auto-injector use and basic life support skills during the first 5 minutes of a severe contrast reaction can significantly improve recognition and knowledge in treating patients having severe contrast reactions. © 2010 AUR.