High-fidelity simulations of patient scenarios have been used successfully to promote critical thinking and staff teamwork in emergency departments, critical care, and medical transport. In contrast, this strategy has been little studied in ambulatory environments. The First Response: The First 10 Minutes, a two-phase, simulation-based education program, was designed to help staff from 21 primary/specialty clinics and five urgent-care clinics improve the immediate care of patients with chest pain or anaphylaxis until the arrival of ambulance crews. Key components included updated standing orders, easy-to-use documentation tools, interactive learning stations with expert faculty, on-site education, and scenarios based on real-life situations with immediate debriefings. The effects of this program on clinic staff were increased knowledge, confidence, and skills that translated into better management of actual patient emergencies. An unanticipated benefit of the in-situ, simulation-based education was the discovery of 40 safety concerns that were readily addressed.