Work on this vast edifice started in late 1574 during the reign of Grand Master Jean de la Cassiere (1572-82) and was extended several times over the years. The “Old Ward” which is the main attraction was extended into the “Great Ward” during the years 1660 to 1666 under the rule of the Cotoners. This hall measuring 155 metres in length, was at that time one of the largest in Europe and was described as “one of the grandest interiors in the world”. The Sacra Infermeria was considered to be one of the best hospitals in Europe and could accommodate 914 patients in an emergency.

In 1676 Grand Master Nicholas Cotoner (1663-80) founded the School of Anatomy and Surgery at the Infirmary. This school was to be the forerunner of the Medical School of the University of Malta. Surgeon (Later Sir) David Bruce discovered the undulant fever germ (Brucellosis) in 1887, when the Hospital was used by the British Military Forces as the Garrison Hospital (1800-1920). During World War II the building suffered serious damages and approximately one third of the complex was destroyed.

When the Order of St John of Jerusalem left the Maltese Islands, the French took over the Infirmary in June 1798, just after the occupation of the Island by General Napoleon Bonaparte. The Infirmary now became known as “Grand Hospital” or “Hospital Militaire”. The French carried out various structural alterations to improve the ventilation, sanitation, and lighting of the hospital. The uprising of the Maltese against the French occupiers on 2nd September 1798 meant the decline of the hospital as drugs, fresh meat, and fruit were no longer available at the hospital. The situation in the hospital and indeed in the whole island was so bad that General Claude H.B. Vanois, the commander in chief of the French forces surrendered the island on 5th September 1800 to the English forces.

From 1800 till 1918 during the British Rule, the Centre served as a Station Hospital. Situated very near to the Grand Harbour, the hospital was within easy reach of the sick and wounded servicemen as hospital ships brought them in. For this reason the Station Hospital was mainly used as a sorting base and also as a centre for dangerously ill patients that could not be moved any further.

The end of World War I saw the end of the Station Hospital. The Infirmary’s Hall was turned into the Police Headquarters from 1918 till 1940. During the ensuring bombardments of Valletta, during World War II, the Mediterranean Conference Centre received four direct hits.

Part of what remained standing of the Long Ward was the Entertainment Centre for the allied troops and became known as the Command Hall, from 1945 till 1950.

Between 1950-1951 it was turned into a Children’s Theatre.

From 1959 the Centre served as a School and Examination Hall.

Several attempts at restoration and reconstruction of the derelict building were made in 1959 and 1975, with a final effort during 1978 when the building was transformed into the present Mediterranean Conference Centre. The Centre was inaugurated on the 11th February 1979, and was awarded the coveted Europa Nostra Diploma of Merit for the “superb restoration of the Sacra Infermeria and its adaption for use as a conference centre.”