Health Minister Edwin Poots is due to cut the first sod on the next development stage at the Ulster Hospital in Dundonald, Co Down.
The £232m development will see a new ward block constructed and also, a new acute services block.
Welcoming the development, Minister Poots said: “The commencement of construction of the new ward block and acute services block mark the beginning of the next vital phase of redevelopment at the Ulster Hospital.
“A number of new facilities, such as the Renal Unit and Critical Care Unit, have already been constructed and are operational on the site.
“A new ward block and acute services block will enhance these facilities further. These modern facilities will be constructed using the latest innovations in design and technology and will be well-equipped to provide secure, safe, high quality services to patients.”
The new ward block, which will replace the existing main ward block constructed in 1962, will cost an estimated £115m and will provide capacity for 288 new beds.
This will facilitate 12 inpatient wards with 24 ensuite rooms offering day surgery, endoscopy, angiography, pharmacy and support services.
The second phase, the new acute services block, will cost an estimated £108m and will provide 170 beds.
The block will include an acute assessment unit, wards, an emergency department and parking.
The ward block is expected to open in early 2017, followed by the acute services block in early 2018.
In 2010, a £53m Critical Care unit was opened by the then Health Minister Michael McGimpsey.