The keys to the Jubilee Building, which contains 112 single en-suite bedrooms, were handed over by construction firm Bam to the Taunton and Somerset NHS Foundation on Thursday.
Trust chairman Rosalinde Wyke said the health authority had first looked almost 30 years ago at the project to replace outdated surgical facilities in the Old Building, which was constructed during the Second World War.
She said: “We should be very proud of the result. It’s been a long project and we’re absolutely delighted we’ve now got it in place.
“It will make a real difference to staff and patients.
“I know that for most patients, single rooms give them privacy and dignity and for many an uninterrupted night’s sleep, as well as shortening their stay in hospital.”
The first patients are due to be operated on in the Jubilee Building by mid March, with the facility likely to be fully operational by the end of the month.
Senior project manager Steve Power said: “This building is one of the reasons I was interested in coming to work at Musgrove five years ago.
“It’s fantastic to see it almost finished and nearly ready for patients to move in.”
Sister Donna Ryan said: “It will make a big difference to the patients and will be a huge change for staff as well.”
Junior sister Kizzy Hamblin said: “We’re very excited and can’t wait to move in.”
Steve Tapson, regional director for Bam Construction, said: “It’s a great sense of achievement. It’s a real collaborative project that’s had an extremely long gestation period.
“It’s very satisfying to see the building completed and everybody’s absolutely delighted with it.”