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The Ulster Medical Society was formed on 30 April 1862 through the amalgamation of three older societies, the Belfast Medical Society which was founded in 1806 and revived in 1822, the Belfast Clinical and Pathological Society which was founded in 1853, and the Ulster Medical Protective Association which was founded in 1859. While the Ulster Medical Protective Association was described by Professor J C Ferguson as having amalgamated with the two earlier ones, in fact its influence must have been minimal. Its name does not appear in the minutes of the amalgamation on 30 April 1862, and, indeed, seems to have been forgotten about for over a century. There may have been competition between the two main societies but there is no record of animosity. Considering the different aims and the commonality of their members it would have been a little surprising if there had been. Both societies were tending to falter and it became apparent that there would be benefit in having one larger society.

The Belfast Medical Society had had its Library in a room on the ground floor of the General Hospital. One of the first decisions the new Society took was to establish a reading room in 33 High Street. Some meetings of the Society were held here, the rest being held in the hospital in what was thereafter described as the pathological room. While it is likely that this move was due to a lack of space in the hospital there may also have been a desire to emphasize the passing of the old and perhaps the new reading room was more convenient or comfortable for the members.

Four years later the Society moved back to the hospital thanks to the generosity of John Charters who had endowed a new wing and had included in the design two rooms in the basement which were fitted out for the Society's use. This was to remain the sole home of the Society until 1884 when, in order to encourage attendance, Council recommended a partial move to the more pleasant surroundings of the Belfast Museum in College Square North, the pathological museum remaining in the hospital. According to Hunter¹, non-members kept interfering with the Society's property and in 1894 it was decided to move to 13 Lombard Street. Two years later, due to the increasing membership of the Society and the inconvenience of the rooms, they moved back. Despite a written agreement with the Museum that the Society's room should be kept locked and users registered, non-members continued to cause problems. In 1901 Council were considering what should be done when events overtook them and they received an offer from Sir William Whitla, then serving as President for the second time, to build and equip at his own expense a Medical Institute to be held in Trust for the Society.

This magnificent building in College Square North was completed in 1903 and remained the home of the Society until 1965. There were a number of reasons why it was given up, perhaps the most important being the location. Where it was built was once a popular place for doctors to live, Whitla himself having a house opposite. With time, however, there was a move away from the area and parking became more difficult. At one time there was some concern about the foundations settling following building work nearby though Whitla said that he intended to have it so well piled that the foundations would withstand another floor being added in the future, and, when it came to be demolished, the contractor said that it was the best-built building he had ever knocked down. Other problems included the expense of running the society and the building (including a salary for the caretaker), and the final straw appears to have been a demand for rates which the Society could not avoid as it was not considered to be a charity at that time.

Under the terms of the Trust, if the Society gave up the building it was to be sold and the money given for specified purposes either to the Royal Victoria Hospital or to Queens University. During his life Whitla himself realised that these conditions were unsatisfactory from the Society's point of view but the Trust deed could not be changed after it had been signed. Queens University agreed that if they received the money they would provide accommodation for the Society in a new building that was being planned and this is how the Society came to have a presence in the Whitla Medical Building. A number of pieces such as windows and stone heads were retrieved from the old Institute and placed in the new Building. During the demolition of the Whitla Medical Institute the pediment was retrieved and is now in place in front of the Whitla Medical Building.

Within the Whitla Medical Building, the society had a council room, large lecture room, cloakroom, kitchen, meeting room, and store room, initially, but erroneously, specified in the governing deed as being for the society's exclusive use. The deed was soon amended to reflect what had been agreed, namely that the council room was for the society's exclusive use, the rest to be shared with the university. Much of the accommodation was under-utilized and in 2009 it was agreed to allow the university to take over a major portion of the space, the society in return being given a larger council room, a storeroom, the shared use of a pair of seminar rooms, and access to a large lecture theatre.

The Ulster Medical Society sent its transactions to the Dublin Journal of Medical Science for about sixteen years and during that time also published four separate volumes of the Transaction of the Ulster Medical Society. These started to appear annually in 1884 and continued to do so until 1928 missing only 1899. The Transactions then ceased and, instead, in 1932, the Society began to publish the Ulster Medical Journal in four issues a year. At the outbreak of WWII the issues were reduced to two a year and this continued until 2006 when they were increased to three. The Journal continues to offer a quality, peer-reviewed window on the world of medicine in Ulster and elsewhere, suitable for novice and veteran author alike.