Abstract The out-of-hospital setting is unique to health care and presents many challenges to providing safe, high-quality medical care in emergency situations. The challenges of the prehospital environment require thoughtful design of systems and processes of care. The unique challenges of ambulance safety may be met by analyzing systems and incorporating process improvements. The purposes of this paper are to 1) outline the nature of this problem, 2) introduce a framework for this discussion, 3) provide expert opinion from a two-day ambulance safety conference, and 4) propose a plan of action to address the safety issues identified in the literature and expert opinion at the conference. Utilizing the Haddon Matrix as a framework, we present the safety issues and proposed solutions for factors contributing to an injury event in the emergency medical services (EMS) transport environment: host, agent, physical environment, and social environment. Host refers to the person or persons at risk, in this case, the EMS personnel or the patient. The agent of injury refers to the energy exerted during the course of an injury, and may be modified to include unrestrained equipment that contributes to the injury. The physical environment refers to the characteristics of the setting in which the injury takes place, such as the roadway or the physical design of the ambulance. Finally, the social environment refers to the social, legal, and cultural norms and practices in the society, such as peer pressure and a culture that discourages the use of safety equipment.