Crash carts are mobile containers of medications and supplies used to resuscitate patients in emergencies within health care facilities. Contents and organization of carts often differ across hospitals and even departments within the same hospital. To support our team members in emergencies across our multi-hospital system, we created a system safety initiative to standardize and optimally organize adult crash carts. Our team established a three-phase user-centered research and design approach. First, we facilitated a collaborative design workshop with front line stakeholders to develop an initial cart organization. Second, 59 clinicians across 8 departments interacted with a cart mock-up and provided feedback. Finally, 18 clinicians participated in usability testing of the updated cart in 3 separate full simulations of realistic patient emergencies including an airway emergency (anaphylaxis), cardiac arrest (ventricular fibrillation), and sepsis using manikins. Observations and feedback from all three research phases contributed to a final medical supply list and crash cart design for our hospital system. This work also provides guidance for using co-design methods and usability testing within hospital environments.