Founders included Thomas Molyneux,  William Petty (physician to Cromwell's army in Ireland and champion of the collection of mortality statistics, such as cause of death),  and Scotsman Sir Patrick Dun, after whom Ireland's first purpose-built teaching hospital was named in 1816.

In the 1700s the college's members established private medical schools and several hospitals in Dublin. Among them were: the Charitable Infirmary, Jervis Street (1718-1987); Dr Steevens' (1733-1985); Mary Mercer's Hospital, on the site of Stephen's Green leper colony (1734-1983); the Rotunda (1745- ); St Patrick's hospital for the insane (1749- ); and the Meath which is now part of Tallaght Hospital.

The RCPI headquarters are in Kildare Street, where they have an interesting collection of historic Irish medical texts and instruments, and even one of Napoleon Bonaparte's toothbrushes.