Following the 1946 national coal strike, the United Mine Workers of America established a Welfare and Retirement Fund to meet the medical needs of miners, their families, and widowed spouses and orphans. The initial program used existing medical facilities. Then in the 1950s the UMW constructed a chain of hospitals as part of the program. Ten were constructed in the Appalachian region, with three hospitals in West Virginia, at Williamson, Man, and Beckley. The hospitals at Williamson and Beckley served as hubs in the interstate system.

The hospitals offered the best medical care available at the time. Accidents in the mines often resulted in spinal cord injuries. The hospitals constructed by the UMW, as well as other hospitals that had participated in the program earlier, gained fame for their advances in treating spinal cord injuries. The union hospitals often served as sites for research or instruction related to these injuries. The hospitals later added nursing schools. The medical program also pioneered intensive vocational rehabilitation programs.

Despite the union's initial enthusiasm for hospital construction, problems soon emerged. The UMW was not prepared for the financial burden and the day-to-day administration of the interstate hospital system, and in the 1960s announced that the chain would be closed. S. M. Kerr, a Presbyterian minister who had worked with the hospital chain in Kentucky, realized the crisis this would create for the rural mining counties. He persuaded the Board of National Missions of the United Presbyterian Church to step in to save the network in 1963. The board formed a nonprofit corporation, Appalachian Regional Hospitals, and bought the hospitals for $8 million using state and federal funds.

In the 1960s and '70s, ARH faced hard economic times and fell into debt. The number of working union miners continued to decline. In 1978, ARH announced it would close its Man hospital. The ARH hired a new administrator, Robert L. Johnson, who brought financial stability to the network by increasing efforts to collect bad debts and raising rates for services.

In 1986, Appalachian Regional Hospitals changed its name to Appalachian Regional Healthcare. As of 2013, the corporation operated eight hospitals in Kentucky and two in West Virginia. The two West Virginia facilities are in Beckley and Hinton. In 2015, Appalachian Regional Healthcare attempted to buy Williamson Memorial Hospital, but the purchase was blocked.