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Cass Regional traces its roots to Harrisonville Memorial Hospital, which was founded on the historic Harrisonville square in 1946. In the early 1960s, the Memorial Hospital Association board began a drive to construct a new facility, and Cass County voters approved a $400,000 bond issue for a new, 50-bed hospital. In 1963, Cass County Memorial Hospital opened at 1800 E. Mechanic St. in Harrisonville.

In 1984, the hospital's name changed to Cass Medical Center to reflect its growing scope of services, and the original hospital building was expanded in 1982, 1988 and again in 1992. In October 2007, Cass Medical Center broke ground on a new, 138,000-square-foot replacement facility at 2800 E. Rock Haven Road in Harrisonville, and in August 2008, the organization was renamed Cass Regional Medical Center to better describe the area it serves. The present facility opened a year later on September 30, 2009.

As part of its mission to provide accessible care to the communities it serves, Cass Regional established family practice clinics in the towns of Archie, Garden City, Harrisonville, Peculiar and Pleasant Hill during the 1990s and early to mid-2000s. In 2010, Cass Regional acquired Kingsville Medical Clinic, formerly Western Johnson County Medical Clinic. Today, more than 75,000 patient visits are experienced annually at Cass Regional and its affiliated locations. With more than 400 employees, Cass Regional is one of the largest employers in the region.

The hospital is owned by Cass County, Missouri, and the organization is governed by a five-member Board of Trustees elected by county citizens. While the Board of Trustees retains governance and operating control, Cass Regional is managed under contract by Healthcare Corporation of America (HCA) Midwest Division. Since 2003, the medical center's administration and other valuable servicesincluding purchasing group membership, managed care contract negotiation and strategic planning serviceshave been provided through this arrangement.

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