This Federal, multi-disciplinary first responder guidance document, developed by the US Department of Homeland Security Office of Health Affairs, translates evidence-based response strategies from the US military’s vast experience in responding to and managing casualties from IED and/or active shooter incidents and from its significant investment in combat casualty care research into the civilian first responder environment. Additionally, civilian best practices and lessons learned from similar incidents, both in the US and abroad, are incorporated into this guidance.