The hospital was formerly known as the Brisbane General Hospital.
The hospital precinct was listed on the Queensland Heritage Register in 2003.
The hospital currently has a total of 948 beds. It is estimated that 65% of the patients served come from 15 kilometres of the hospital.
In January 2008 there was a public health scare over concerns about lead levels at the Royal Brisbane and Women's Hospital. Lead tests carried out at a Brisbane hospital found levels were safely below recommended standards. Queensland Health said there was no need to worry about children being exposed to lead at the Royal Brisbane and Women's Hospital after air and surface swabs returned results below the levels recommended by the Environmental Protection Agency (EPA).
In February 2008 the hospital was hit by a "super bug" outbreak. The bacteria, known as Vancomycin resistant enterococci or VRE. The hospital closed two 30-bed wards to new admissions in early December after 21 patients tested positive to VRE. Nurses were forced to take extreme measures to stop the bacteria spreading.