After suffering a humiliating Commons defeat, helped by 39 Coalition rebels, the Prime Minister acknowledged "politics is difficult" but made clear he would not have to apologise to US President Barack Obama for being unable to commit UK military units to any international alliance.
Stressing it was vital to maintain the international ban on chemical weapons, he said: "We will continue to take a case to the United Nations, we will continue to work in all the organisations we are members of - whether the EU, or Nato, or the G8 or the G20 - to condemn what's happened in Syria."
His parliamentary setback came despite watering down his original Commons motion to promise a second vote on military action. Tory HQ had railed against Ed Miliband, accusing him of playing party politics on Syria and "flip-flopping" on the issue of military strikes.
Asked if the Labour leader had behaved "dishonourably", Mr Cameron said: "It's a matter for him to defend the way he behaved and his conduct."
Mr Miliband, who had denounced the PM's leadership on Syria as "reckless and impulsive", insisted Mr Cameron would now have to "find other ways" to put pressure on the Assad regime.
Stressing that the Coalition should not wash its hands of the issue, he said: "There are other routes than military means to actually help the people of Syria," mentioning diplomatic and political pressure.
In the aftermath of the vote, there was a good deal of recrimination and political reflection.
While the PM said the Government whips had done a "good job", his view was not shared by some of his Tory colleagues.
Pressure was mounting for him to sack Sir George Young, the Chief Whip, as 10 ministers and government aides together with a raft of other Coalition MPs did not turn up for the key vote; if they had the Government would have won.
One Tory MP insisted: "George Young has got to carry the can for this."
It was suggested the bicycling baronet could be for the chop in a forthcoming Cabinet reshuffle.
In political reaction to the vote, Lord Ashdown, the former Liberal Democrat leader who was the High Representative in Bosnia, said the UK was "hugely diminished" by it.
The peer said he had never felt more ashamed or depressed following the Commons vote, which, he said, was "a bad night for the Government and a bad night for Britain too".
But backbencher Sarah Wollaston, one of the Tory rebels, insisted the reverse inflicted on the Prime Minister was a "good day for Parliament" as it reflected the widely-held view across Britain against military intervention.
Angus Robertson, for the SNP, insisted that after the UK Government defeat there had to be a renewed diplomatic and humanitarian focus and a specific initiative to bring those who had used chemical weapons before justice.
"The international community must prioritise efforts for a comprehensive peace settlement in Syria including justice for the victims of alleged chemical weapons attacks," he said.
Meanwhile, George Osborne accepted the Coalition defeat would spark a debate about whether Britain still wanted to play a major role in the world.
"There will be a national soul-searching about our role in the world and whether Britain wants to play a big part in upholding the international system," said the Chancellor.
When asked whether the parliamentary defeat would damage Britain's alliance with America, he replied: "There's a bit of hyperbole on this in the last 24 hours. The relationship with the United States is a very old one, very deep and operates on many layers."