Preparation for construction will begin immediately.
The project is one of five healthcare projects being procured under the Scottish Government’s non profit distributing model.
O’Rourke is part of the High Wood Health consortium with Serco who will provide estate management services.
The European Investment Bank is putting up a 26-year £109m loan to build the new hospital.
Dennis O’Keeffe, NHS Dumfries and Galloway Project Director for the new hospital said: “It has been a pleasure to partner with High Wood Health as our preferred bidder and together we have reached financial close in record time for a project of its scale and complexity.”
Laing O’Rourke’s David Hunter, also Bid Director for High Wood Health, said: “With financial close now achieved, High Wood Health and our partners are looking forward to progressing in earnest with the construction works onsite – meaning the next phase in this landmark project can begin.”