Named after King Charles III at that time as Prince of Wales, and officially opened on 1 November 1982 by Katharine, Duchess of Kent, the hospital went into operation on 1 May 1984.

The plan was to allow the first batch of medical students admitted in October 1981 to start their clinical training at the hospital in July 1983.

[5] Until the mid-1990s, the hospital was responsible for providing medical services to the nearly 25,000 Vietnamese boat people at Whitehead Detention Centre in nearby Wu Kai Sha, once considered the world's largest prison.

[9][10] By 1994, some Sha Tin residents voiced dissatisfaction that their hospital bore the weight of the refugee's medical needs, but then-hospital chief executive Alison Reid responded that the boat people comprised only five per cent of monthly visits to A & E and that the local population was "not being disadvantaged".

With a total floor area of 7,930 square metres, the clinic provides additional space to cope with increasing demand for specialist outpatient services in the region.

The epidemic in Hong Kong started with the outbreak in Prince of Wales Hospital on 10 March 2003 when 11 healthcare workers in ward 8A (later renamed 8H) had shown symptoms of atypical pneumonia at the same time.

The dirty team, led by Professor Joseph Sung, was responsible for taking care of SARS patients.

The Main Clinical Block and Trauma Centre, a fourteen-storey new building, was built on the site of the original helipad and tennis court.

[26] In November 1987, Prince of Wales Hospital delivered the first baby from gamete intrafallopian transfer in Hong Kong.

[29] In February 1991, the first twins resulting from pronuclear stage tubal transfer (PROST) in Hong Kong was born at the hospital.

PROST is a technique that involves in vitro fertilisation (IVF), followed by transfer of the pronuclear oocytes into the fallopian tubes.

The station is on the Tuen Ma line, providing a direct link from the hospital to different areas in the Sha Tin District.

[40][41] An oncology trainee erroneously injected a leukaemia patient with the chemotherapy drug, vincristine, via the intrathecal route instead of intravenous on 15 June 2007.

[42] The patient was prescribed six oral drugs, intrathecal cytarabine and intravenous vincristine by another doctor, and was injected by the trainee later the day.

The woman attended the Accident and Emergency Department of the Prince of Wales Hospital on 8 July due to shortness of breath and was admitted to the medical ward.

The admission resident doctor prescribed the patient with her usual medications (including aspirin, calcium carbonate, Lasix and Pantoloc).

An investigation found that the intern perceived that the instruction was to resume the patient's usual medication in addition to those already prescribed on the record.

She mistakenly transcribed five medications (including Candesartan, Gliclazide, Metformin, Betaloc and Isordil) intended for another patient onto the record.

Three of the women had their episiotomy repair done by an intern in June, and the fourth woman was treated by a resident doctor in July.