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St Vincent's Hospital, Sydney is located in the inner city suburb of Darlinghurst. It was originally established in 1857 by five Irish Sisters of Charity, who had migrated to Sydney in 1838 with a mission to help the poor and disadvantaged. Some of their early work included helping victims of the 1844 influenza outbreak, and prisoners and their families of the nearby Darlinghurst Gaol. Three of the Hospital's founding Sisters had trained as professional nurses in France, and they brought their knowledge to the colony, establishing a hospital that was free to all people, but especially for the poor. The original site for the hospital was in the neighbouring suburb of Potts Point. As demand grew, the establishment was moved to its present location in Darlinghurst in 1870. The hospital celebrates its sesquicentennial birthday in 2007.

St Vincents Hospital is today, a leading medical, surgical and research facility. It has been at the forefront of innovation in areas such as heart, lung and bone marrow transplantation. The hospital was also one of the first health care facilities in Australia to start treating AIDS patients, a direct result of its close geographic position to the predominantly gay areas surrounding nearby Oxford Street, Sydney. As the AIDS epidemic grew in Sydney, the hospital led the way in the compassionate treatment of the sick and the dying, continuing to apply the original values of the Sisters' Mission. This early exposure to the frightening implications of a possible epidemic, was responsible for St Vincents becoming one of the leading centres of immunology research and practice in Australia. The immunology ward of the hospital was also strongly supported by the local gay community, who staged numerous charity events to raise money for AIDS care. In 1996, St Vincents joined the Sisters of Charity Health Service, which already encompassed 17 other health care facilities, and which is now, Australia's largest not-for-profit health care provider. The hospital is a principal teaching centre and has close affiliations with a number of universities including University Of New South Wales, University of Technology, Sydney, Australian Catholic University and the University of Notre Dame Australia.

As of 2007, the hospital comprises over 360 medical and surgical beds. The Emergency Department was one of the first in NSW to implement a PECC (Psychiatric Emergency Care Centre), in response to the high number of people with a mental illness residing in the inner suburbs of Sydney, as well as the increasing incidence of people affected by illegal, psychoactive drugs such as heroin, GHB and crystal meth. In line with the Sister's original mission, the hospital oversees the largest population of homeless people in Australia, concentrated in the neighbouring suburbs of Kings Cross, Surry Hills, and Woolloomooloo. Paradoxically, the hospital's catchment area also includes some of Sydney's, and indeed, Australia's most affluent suburbs, including Vaucluse, Paddington, Bellevue Hill, Rose Bay, Point Piper and Darling Point.

The St Vincents Campus encompasses St Vincent's Private Hospital, Sydney, Sacred Heart Hospice, The Mater Hospital, Sydney, The Garvan Institute of Medical Research, The Victor Chang Cardiac Research Institute and the National Centre in HIV Epidemiology and Clinical Research.

The hospital is a part of the South Eastern Sydney Illawarra Area Health Service. It is also a recognised trauma centre, resulting in the majority of major trauma cases that occur close to the inner city being referred to St Vincents, despite Sydney Hospital being geographically closer to Sydney's central business district.