Lockerbie bomber Abdelbaset Ali al-Megrahi has died in Tripoli, his brother said on Sunday.
Megrahi was sentenced to life in prison for the 1988 bombing of a US airliner over the Scottish town which claimed 270 lives.
He was released from jail on August 20 2009 on compassionate grounds after being diagnosed with terminal prostate cancer and sent home to Tripoli with an estimated three months to live.
His death at his Tripoli home at the age of 59 was announced today by his son, Khaled.
David Cameron said: "Today is a day to remember the 270 people who lost their lives in what was an appalling terrorist act.”
"Our thoughts should be with them and their families for the suffering they've had."
The Prime Minister dismissed calls for an inquiry into Megrahi's conviction which Libyans always contested.
"This has been thoroughly gone through," he said.
"I'm very clear that the court case was properly done and properly dealt with."
The decision by Scottish Justice Secretary Kenny MacAskill to free the only man convicted of bombing of Pan Am flight 103 provoked an international storm.
The bombing of the American plane, travelling from London to New York four days before Christmas, killed all 259 people on board.
Eleven residents of the Dumfries and Galloway town also died after the plane crashed down on their homes in Britain's biggest terrorist atrocity.
After protracted international pressure, Megrahi was put on trial under Scots law at Camp Zeist in the Netherlands.
He was found guilty in 2001 of mass murder and was ordered to serve a minimum of 27 years behind bars.
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Despite claims that he could not have worked alone, and the lingering suspicion by some that he was innocent, Megrahi was the only man ever convicted over the terrorist attack.
He was freed from prison having served nearly eight years of his sentence after he dropped his second appeal against conviction at the Court of Criminal Appeal in Edinburgh.
MacAskill's decision to allow him to return home to die in Libya sparked international condemnation from some relatives of victims and politicians, who demanded he be returned to jail.
US families were among the most vocal critics of the decision, along with US president Barack Obama. US secretary of state Hillary Clinton branded the move "absolutely wrong".
American fury at the decision was compounded by the hero's welcome Megrahi received in Tripoli upon his return.
Prime Minister David Cameron has also come under pressure from some US senators for an independent inquiry into the decision to free the bomber.
But the move attracted support from some victims' relatives in Britain, and high profile figures such as Nelson Mandela and Archbishop Desmond Tutu.
David Ben-Ayreah, a spokesman for the victims of Lockerbie families, said: "I was told seven days ago by very good sources in Tripoli that he was slipping in and out of quite deep comas, that the secondary tumours had affected his abdomen and lower chest, and that he had had three blood transfusions.
"His death is to be deeply regretted.
"As someone who attended the trial I have never taken the view that Megrahi was guilty.
"Megrahi is the 271st victim of Lockerbie."
An undated Crown Office handout of Abdelbaset Ali Mohmed Al Megrahi, who was convicted of the Lockerbie bombing.
Scotland Office Minister David Mundell, whose Dumfriesshire, Clydesdale & Tweeddale constituency includes Lockerbie, said:
"Obviously, one commiserates with family members at the time of a death, whatever the circumstances.
"Mr Megrahi's passing is the end of a chapter, but not the end of the story that has unfolded since that terrible night in 1988.
"It will not bring closure to all those bereaved or otherwise caught up in that tragic event and who want answers.
"So, that quest goes on and I still hope that the new regime in Libya can play a part in delivering those answers.
"I recently visited Syracuse University in New York State.
"Thirty five Syracuse students died in the Lockerbie bombing and it is they and all the other 270 victims that should be and remain in our thoughts."
A scene of devastation in Lockerbie, Scotland after PamAm flight 103 was bombed, killing 270 people.
In August 2009, Mr MacAskill told the world that cancer sufferer Megrahi was going home to die amid suggestions he had about three months to live.
The Justice Secretary acted on the basis of a medical report provided to him by Dr Andrew Fraser, the director of health and social care at the Scottish Prison Service.
His report described the three-month prognosis as "reasonable", but stated that no-one "would be willing to say" if Megrahi would live longer.
Megrahi's death comes two years and nine months after his release from Greenock prison.
Scottish ministers have always insisted that their decision was made in good faith, on compassionate grounds alone and followed the due process of Scots law.
But those who opposed the decision insisted that Megrahi should not have been freed from jail in Scotland.
With each anniversary connected to Megrahi's controversial release, calls were repeated for an apology from the Scottish government and for more evidence to back up the decision.
Consultant urologist professor Roger Kirby, founder and director of The Prostate Centre in London, said he believed that abiraterone was likely to have been responsible for Megrahi's prolonged life well beyond the three-month point.
Last month Megrahi was reported to have been admitted to hospital for a blood transfusion.
Despite sparking international controversy, and a vote symbolically rejecting the decision in the Scottish Parliament, Megrahi's release from prison appeared to have had no effect on the SNP's fortunes.
The party, with MacAskill, was returned to power at Holyrood in a landslide victory in May last year.