The proposed Aberdeen bypass can go ahead, Supreme Court judges in London have ruled.
Campaigner group RoadSense has been fighting to stop the £400m route which would join the A90 from Blackdog to Stonehaven.
The group said the decision "would seem to bring to an end" its legal challenge.
The near 30-mile planned road - known as the Aberdeen Western Peripheral Route (AWPR) - was given approval by Scottish ministers in 2009 following a public consultation which RoadSense claimed was flawed.
First Minister Alex Salmond said that work would begin immediately with drilling works starting next month and a completion date of 2018 set.
He said: "The decision by the Supreme Court is a just ruling for the north east of Scotland and an opportunity for Scotland that marks the end of five incredibly frustrating years for the vast majority of people who are behind this ambitious project.
"Over the next three decades, the AWPR and the Balmedie to Tipperty road schemes are expected to bring in an additional £6bn to the local economy, creating around 14,000 new jobs. It is therefore crucial that we crack on and deliver these vital and frankly long overdue infrastructure projects.
"The minority who have held up the AWPR have had many days in court – not to mention a protracted public local inquiry – and they have lost on every occasion. Now that their challenge has come to an end, our focus is now to move on from these unwanted legal problems and make quick progress for the people of the north east – they have waited long enough."
Two appeals against the final route by the group have already been thrown out by judges in Scotland.
William Walton, who led the group, said: "Obviously this is not what I had hoped for, or expected. I have always maintained that the route selection process was flawed and that people living along the Fast Link were deprived their rightful opportunity to be consulted. Clearly the Court has come to a different view. Nevertheless I take some comfort from the Court's view that the action was legitimate".
A RoadSense spokesperson said: “RoadSense members will obviously be disappointed at today’s outcome. The proposed route of the AWPR will have a devastating impact on the homes and livelihoods of many of our members and we remain firm in our belief that the road will not deliver its promised benefits.
"We have always believed that the beautiful areas of green belt that surround our city are precious and should be properly safeguarded as an amenity for our and future generations to enjoy. Nothing in today’s judgement changes that.
"Subject to advice from our lawyers, this would seem to bring to an end our attempts to overthrow the Minister's decision to approve the AWPR through the courts. Nevertheless I am sure that RoadSense will continue to oppose the scheme in whatever ways we can."
Politicians have welcomed the courts decision.
North-east MSP Alex Johnstone said: “This is a project which should have been nearing completion by now, not languishing in the courts, tied up in legal process.
“The only positive thing Walton has achieved is demonstrating that the planning process which he has challenged so successfully, is not fit for purpose.”
It is estimated the route will boost the north-east economy by £4.25bn by five years after completion.
Aberdeen City Council leader Barney Crockett said: "This marks the end of a long, drawn-out process, and we have waited years to get to this stage, but we are very pleased with the Supreme Court's decision. We can now start making progress on a project which is critical, not just for the economic future of the area, but for the whole of Scotland.
"Now we have to get on with the job of creating the traffic infrastructure in the north-east which is crucial to maintaining and enhancing Aberdeen's reputation and providing a road network for the 21st century."
Aberdeenshire Council's leader Jim Gifford has also welcomed the decision.
According to estimates when complete the road should remove around 5% of traffic from travelling through Aberdeen city centre and north-east MSP Lewis Macdonald called for the government to have “shovels in the ground before Christmas”.
Not all politicians welcomed the decision with the Greens calling the result "disappointing".
Patrick Harvie MSP, co-convener of the Scottish Greens, said: "This ruling is disappointing but at least the judges acknowledge that the bypass is bound to have a significant impact on the environment. Now it seems the public purse will have to cough up a staggering £400m for a system of roads that will simply encourage more traffic, contradicting Scotland's low carbon ambitions and doing little to reduce congestion in Aberdeen city centre.”
He said the city” would be much better served by decent public transport”.
The decision is also good news for other projects tied into the AWPR including improvements to the A90 north of Aberdeen and the city’s notorious Haudagain roundabout.
MSP for Aberdeen Donside Brian Adam said he was delighted by the court’s decision. He said: "Not only is this a landmark moment for the AWPR, but this also hopefully marks the start of the countdown to improvements on the Haudagain."
MP for Gordon Sir Malcolm Bruce added: “The Scottish Government now needs to proceed to construct this vital route as soon as possible and stop needlessly delaying the Balmedie-Tipperty A90 upgrade.”
MSP for Aberdeen Central Kevin Stewart said he was “relieved” by the decision and that it would be a “travesty for democracy” if the protestors were allowed to take their fight to the European Court of Justice.