The origins of the hospital go back to the Belfast General Hospital which was based on Frederick Street in the north of the city. By the 1890s further expansion on that site was impossible and fundraising began to develop a new modern hospital led by William James Pirrie (uncle of Lord Pirrie, chairman of Harland & Wolff, the famous Belfast shipyard).
The new hospital was designed by architects Henman & Cooper and was the first hospital to have a plenum air-conditioning system, pioneered by Samuel Davidson and his Belfast engineering company Sirocco works.
The Royal Victoria Hospital emerged as a world-renowned centre for medical treatment; for example, research at the hospital was instrumental in the creation of the first portable defibrillator invented by the Ulster physician and cardiologist Frank Pantridge in 1965.
Forced by necessity, the medical staff became pioneers in the treatment of injuries particular to the type of violence occurring in the north of Ireland during the conflict. These included injuries from plastic bullets, punishment beatings, high velocity shot gun wounds and explosions such as shrapnel damage, burns and loss of limbs or sight.
The original Royal building is of Victorian architecture, but during the 20th century more functional buildings have been built alongside during numerous extensions of facilities. Hospital security was increased during the conflict, with the installation of bulletproof glass and doors.