The Welsh Government has earmarked almost £77 million for the development.
The hospital has already benefited from £7.1million to remove asbestos and for fire safety measures and £5.44million for new operating theatres and a urology day care unit. The Welsh Government has funded these developments.
When the hospital was built in the late 1970s asbestos use was commonplace as a fire retardant coating on structural steelwork.
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The new plans by Betsi Cadwaladr University Health Board – which runs Ysbyty Glan Clwyd – aim to ensure the hospital meets the latest fire and health and safety standards and provide opportunities to remodel the hospital to bring together services that are currently spread over the site.
The Health Board will develop its proposals further in the Outline Business Case.
Ms Griffiths said: "Ysbyty Glan Clwyd has, and will continue to have, a key role in delivering health services in North Wales. Once completed, this investment will significantly improve the care for patients and the working environment for staff.
"We are maintaining our investment in the health service across Wales in cash terms over the next three years – despite the impact of the UK Government’s cuts to the Welsh budget."
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