Thomas Frist Sr. received his undergraduate education from the University of Mississippi and his medical degree from Vanderbilt University in 1933. In 1968, in partnership with his son, Dr. Thomas Frist Jr., Jack Massey, Gene Kidd, and Henry Hooker, Frist founded Hospital Corporation of America, the largest private operator of health care facilities in the world, taking the company public in 1969. The company merged with Columbia Healthcare Corporation in 1993.

Frist was Associate Clinical Professor of Medicine, Emeritus, at Vanderbilt. A nationally known cardiologist and internist, Frist served as personal physician for six Tennessee governors. In 1985, the first fully endowed professorship in internal medicine was established in his name at the School of Medicine. Frist passed away in 1998.