West Virginia University Medicine, which separated from the university in 1984 to become a nonprofit corporation, is the largest private employer in West Virginia.

It expanded from its original J. W. Ruby Memorial Hospital (operated from 1960 to 1988 as University Hospital) to include WVU Medicine Children's Hospital, Chestnut Ridge Center, the Mary Babb Randolph Cancer Center, and the Jon Michael Moore Trauma Center, all on the Robert C. Byrd Health Sciences Center campus of West Virginia University in Morgantown. In addition the WVU Medicine network now includes United Hospital Center in Bridgeport, Camden Clark Medical Center in Parkersburg, Berkeley Medical Center in Martinsburg, Braxton County Memorial Hospital in Gassaway, Fairmont Medical Center in Fairmont, Grant Memorial Hospital in Petersburg, Jackson General Hospital in Ripley, Jefferson Medical Center in Ranson, Potomac Valley Hospital in Keyser, Princeton Community Hospital in Princeton, Reynolds Memorial Hospital in Glen Dale, St. Joseph’s Hospital in Buckhannon, Summersville Regional Medical Center in Summersville, Wetzel County Hospital in New Martinsville, Wheeling Hospital in Wheeling, Thomas Memorial Hospital in South Charleston, and Welch Community Hospital. In 2024, it converted Thomas’s St. Francis Hospital facility in Charleston into West Virginia’s first full-service and comprehensive orthopedic hospital. It also maintains medical centers in Maryland, Ohio, and Pennsylvania.

Ruby Memorial, which opened in 1988, is a 690-bed hospital named in honor of Hazel Ruby McQuain and J. W. Ruby. The facility includes a day surgery center, comprehensive cardiac care, and the most modern medical imaging system in the state.

WVU Medicine Children's Hospital was originally located on the sixth floor of Ruby Memorial Hospital. In 2022, it relocated to a new eight-floor 150-bed facility. It is devoted to all aspects of care for women and children. It houses the area's only neonatal and pediatric intensive care units.

Chestnut Ridge Hospital, a 72-bed psychiatric and chemical dependency facility, opened in 1987. This mental health facility offers inpatient adolescent and outpatient child/adolescent services. Health South MountainView Rehabilitation Hospital, also on the campus, has the largest pediatric rehabilitation unit in the region.

The Jon Michael Moore Trauma Center was named in memory of the 16-year-old grandson of West Virginia's long-time U.S. Senator Robert C. Byrd. The boy died as the result of a car accident. The center is the only Level I trauma center in the region. The Health Net helicopter is dispatched from the radio center at the facility, and complex emergency surgeries are performed on a regular basis. Trauma surgeons, nurses, and other staff members work together to coordinate patient care before and during their transportation from accident scenes. The center cares for more than 3,000 trauma patients annually.

The Mary Babb Randolph Cancer Center is the flagship of the WVU Cancer Institute, which also includes the Betty Puskar Breast Care Center, cancer centers at many of its other facilities statewide plus the Cancer and Infusion Center at Roane General Hospital in Spencer, the Comprehensive Breast Care Program, and the Bonnie’s Bus Mobile Mammography Program (named for Bonnie Wells Wilson), and the Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia’s only source for blood and marrow transplants.

The Morgantown Ronald McDonald House, completed in September 1990, provides low-cost lodging for families of children who are patients at area hospitals. It is operated by an independent local board. About 90 percent of the families staying at the Ronald McDonald House have a child staying at WVU Children's Hospital. The Rosenbaum Family House offers low-cost hotel-style rooms and apartments as on-site overnight lodging for adult patients and families. The structure, near Ruby Memorial Hospital, opened in 1999. With the planned expansion of Ruby Memorial Hospital, Rosenbaum Family House will move to a larger facility adjacent to the Ronald McDonald House.

WVU Hospitals serves as a teaching hospital and training facility for the university's five health sciences schools, dentistry, medicine, nursing, pharmacy, and public health. Nursing and medicine, particularly, use the hospital for clinical instruction of students. WVU Hospitals operates as a nonprofit corporation affiliated with West Virginia University and belong to the West Virginia United Health System.