Michael Gove has told the BBC the vote on the EU referendum was “not a humiliation” for the Conservatives.
In total, 81 Tory MPs, including two tellers, defied the whips, two actively abstained by voting both ways and a further 12 are known not to have voted.
The education secretary said that the government and MPs were “united” behind a goal to get back powers from Europe.
He denied there were “convulsions” in the party and said disagreements had been conducted with “cordiality”.
The backbench motion – prompted after a petition was signed by more than 100,000 people – was defeated by 483 votes to 111, after all Tory, Lib Dem and Labour MPs had been instructed to oppose it.
It called for a referendum on whether the UK should stay in the EU, leave it or renegotiate its membership – but even if the government had lost, it would not have been obliged to hold a referendum.
However Mr Cameron urged his MPs to vote against it arguing that, with a “crisis” in the eurozone: “This is not the time to argue about walking away. Not just for their sakes, but for ours.
“Legislating now for a referendum, including on whether Britain should leave the EU, could cause great uncertainty and could actually damage our prospects of growth.”
But almost half of his backbenchers appear to have ignored his calls.
As well as the 81 who supported the referendum motion, two MPs – Mike Wetherley and Ian Stewart – actively abstained by voting in both the yes and no lobbies.
A further 12 MPs did not vote – although that figure includes Foreign Secretary William Hague, who left the debate early to travel to Australia, and another minister Mike Penning, who was in China.
It was the biggest rebellion against a Conservative prime minister over Europe – the previous largest was in 1993, when 41 MPs defied John Major on the Maastricht Treaty.
But Mr Gove told BBC Radio 4’s Today programme that while there were a “significant number” of rebels – the differences between them and the Conservative frontbench could be “exaggerated”.
“It was a very precisely worded motion which allowed a number of people like myself, who are passionate Eurosceptics, to say: Look, I disagree with the tactics but we agree on the ultimate goal.
“If you have a disagreement about tactics… and if you have that disagreement conducted with cordiality and good manners on all sides then I don’t think it leads to the sorts of convulsions that many people want it to.”
Labour leader Ed Miliband described the result as “a humiliation for the prime minister”: “If he can’t win the argument with his own backbenchers, how can the country have confidence that he can win the arguments that matter for Britain?”
But Mr Gove told the BBC: “It’s not a humiliation …because we have a coalition, all parties need to compromise in the national interest.”
He said the prime minister was “committed” to taking back powers from Europe to boost economic growth in the UK.
Pressed on when that might happen, he said it would be wrong to explain “tactics” in advance of negotiations but added: “I’d like to see that change in this Parliament.”
“We are already winning powers back. We need to win more and that process will require careful negotiation but we are fortunate in having a Conservative Party that is united as never before behind that renegotiation.”
Conservative backbenchers voiced their dismay at the three-line whip in Monday’s vote – the strongest order a party can give – which meant any Conservative MP who voted against the government would be expected to resign from government jobs.
Two Parliamentary private secretaries, Stewart Jackson and Adam Holloway, rebelled. Mr Holloway resigned while Mr Jackson was sacked from the unpaid government post.
One Liberal Democrat MP, Adrian Sanders, defied his party’s leadership and voted for a referendum.
Nineteen Labour MPs rebelled, including Frank Field, Kate Hoey, Jon Cruddas and Graham Stringer. Caroline Lucas, the only Green MP in the Commons, also voted for the motion, as did all eight DUP MPs and independent Lady Sylvia Hermon.
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