Greenville County EMS is a third-service municipal department responsible for providing primary 9-1-1 emergency medical response across 795 square miles within Greenville County. Established in 1975, it remains South Carolina's largest and busiest EMS system. The service operates with a dual-tiered approach, offering both advanced life support (ALS) and basic life support (BLS) ambulances. Each Type-1 extended cab ambulance is equipped with high-end warning systems, cutting-edge mapping software to optimize response and hospital transport routes, and the Power LOAD system for safer and more efficient stretcher handling, promoting patient safety and employee well-being.

The department utilizes a flexible deployment strategy and scheduling to adapt to community demands. Its Mobile Area Routing Vehicle Location Information System (MARVLIS™) strategically forecasts call locations and times around the clock, allowing for optimal ambulance positioning. In addition, Greenville County has 31 fire departments that provide varying levels of medical first responder care, typically at the EMT level. Fire departments certified as Rapid Responder agencies receive oversight from the EMS medical director and participate in the continuing education program administered by Greenville County EMS.

There are two major hospital systems in Greenville County, Bon Secours St. Francis Health and Prisma Health. Bon Secours operates two acute care facilities and a freestanding emergency department. Prisma Health operates four hospitals, including a level-1 adult and level-2 pediatric trauma center, as well as a tertiary referral center. In addition, Prisma has two 24-hour percutaneous coronary intervention centers, one comprehensive stroke center, three primary stroke centers, and a level III neonatal intensive care unit.