The 350-bed hospital will also include 104 staff residencies, a helipad and almost 1,000 parking spaces.
NHS Dumfries and Galloway said it hopes work will begin on the project in 2015 at a site near the town's bypass at Garroch Farm.
Mott MacDonald’s Glasgow office has been signed up to provide technical and procurement advisory services throughout the project development, while procurement is expected to start in the summer.
The final decision on the business case will not be revealed until the end of the year.
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If plans are approved, the contract to build a new Dumfries and Galloway hospital will be let in Autumn 2014.
Julie White, Chief Operating Officer with NHS Dumfries and Galloway, said: "This is an extremely important milestone in the development of a new hospital for this region. The approval by Scottish Government enables us to proceed to the open market to commence our procurement process.
"We will now engage with external companies who will work with us to complete the detailed design, build the hospital and finance the construction.
"The project has already attracted a considerable amount of interest from a range of multi-national companies. The procurement process will take a number of months and it is anticipated that work will commence on site in the Spring of 2015 with the new hospital being open to patients in the first half of 2018.
"This project represents a significant boost to our local economy and we will work with the preferred bidder to ensure involvement of local small and medium sized businesses, and to develop local apprenticeships."
(JP/CD)
