Speaking at the end of a summit of EU leaders that secured the first part of a banking union, Cameron played down fears Britain's future lies on the margins of a two-tier Europe, while euro zone members build an ever-stronger core.
"I don't think Britain is in an uncomfortable position at all," he told a news conference in Brussels at the end of the two-day summit. "We're in a position where we have opportunities to maximise what we want from our relationship."
Cameron, trailing in the polls before a 2015 election, is under pressure from the anti-EU camp in his ruling Conservative Party to reshape Britain's role in Europe or leave the bloc all together after nearly 40 years in the union.
Along with the sluggish economy, Britain's ties with Europe will be one of the fiercest battlegrounds in the election. Polls suggest around half of Britons want to leave Europe and a third want to stay in, with the number of those who want out rising.
Cameron said the summit deal on banking supervision was a sign of the huge changes that lie ahead for the euro zone, a club that Britain does not want to join. Those reforms must be matched by a shift in Britain's position in Europe, he said.
"It will lead to opportunities for us in the UK to make changes in our relationship with the European Union that will suit us better, which the British people will feel more comfortable about," Cameron said.
Decades of division
In a sign of the sensitivity of the EU debate, Cameron has again delayed a setpiece European speech that was due to lay out his views on a subject that has divided the country for decades.
Cameron rejects the idea of an "in or out" vote in favour of a referendum on a new role inside the EU, Britain's biggest trading partner. Under a law passed in 2011, a major transfer of power from London to Brussels in any change to the EU treaty must be put to a public vote.
His talk of a new deal for Britain in Europe may not be sufficient to silence his party's eurosceptics, a powerful group that helped to bring down the Conservatives' last two prime ministers, Margaret Thatcher and John Major.
Anti-EU rebels gave Cameron his first major parliamentary defeat in October in a vote calling for EU budget cuts. The increasingly popular UK Independence Party, a fringe group that wants Britain to pull out of Europe, is also a threat.
Cameron must tread a delicate line between talking tough on Brussels to appeal to eurosceptics, and striking a conciliatory tone that will play well with often exasperated EU neighbours and his pro-EU coalition partners, the Liberal Democrats.
In stark contrast to a summit last December when Britain was isolated after blocking a deal on closer fiscal ties, Cameron's role this time was more low key.
"This wasn't really our fight," one British official said, referring to London's position outside the euro zone.