By 1845, the classes and patients of the medical school moved to the Egyptian building, one of the United States' oldest examples of Egyptian architecture, which is still in use for classes today. In 1854, the Richmond Department of Medicine broke away from its roots in Hampden- Sydney College and became an independent institution known as the Medical College of Virginia.

At the onset of the Civil War, the first state-funded hospital was erected across the street from the Egyptian Building. This hospital, as well as 13 other Richmond facilities, became home to the Confederate Army. One of MCV's doctors, Dr. Hunter McGuire, was General TJ "Stonewall" Jackson's personal physician. The turmoil of war, inflation and worthless Confederate currency caused MCV hospital to sacrifice its ambulance horse for enough money to remain operating.

MCV survived the war, and moved to the forefront of clinical treatment with the introduction of the syringe, thermometer, vaginal speculum, cystoscope, and local anesthesia in 1874. Prior to anesthesia, surgery was performed in patient rooms with chloroform, and surgery could only be performed in the winter months because cholera, typhoid, and diphtheria made the population too weak to sustain an operation during the summer months. Also in 1874, through the binocular microscope, doctors saw for the first time that inflammation and blood cells were required for healing - so they at last abandoned the centuries-old practice of blood letting.

The most significant event of the following 25 years was the initiation of surgical antisepsis. Spraying operating rooms with carbolic acid had been introduced 14 years earlier by Lister in England, but its adoption was delayed in Virginia, under the notion that the pure country air of Virginia was in itself an antiseptic.

In 1900, the college became the first in the country to expand the medical school curriculum to four years, as opposed to the four month curriculum when the college first began. In 1918, Innis Steinmetz, class of 1920, became the first woman to enter the medical school, and thirty years later, the college admitted its first black student, Jean Harris. She later became Virginia Secretary of Health and Human Resources.

In 1925, Dr. Sanger took over as Dean of the SCHOOL OF MEDICINE and brought new buildings to the MCV campus. During the depression in 1932, Tompkins-McCaw library was built. In 1941, the South Hospital was built for 2.5 million dollars with a donation from the Public Works Administration under Roosevelt's New Deal. In 1952, Randolph Minor Hall was completed. The building is named for Agnes Dillon Randolph, the granddaughter of Thomas Jefferson, and Nannie Jacqueline Minor, both girls were students at the School of Nursing. In 1963, Sanger Hall was completed in honor of the dean of the school of medicine, and Main Hospital was finished in 1982. In 1983 the Massey Cancer Center was built, and expansion of North Hospital was completed in 1986.

In 1968, MCV joined with Richmond Professional Institute to form the Medical College of Virginia of Virginia Commonwealth University. It serves as a Level I Trauma Center and a referral center for the Southeast. With 847 physicians, 1093 licensed beds, annual inpatient admissions of more than 35,000, ER admits for 111,000 and outpatient clinic visits of close to 350,000, MCV is the eighth largest medical center on an academic campus in the country.