Leo Varadkar has said that if the UK wants to change its mind over Brexit, it would be welcomed back like the "prodigal son".
The Taoiseach said the United Kingdom would be welcomed back to the European Union "with open arms".
Mr Varadkar made the comments to the US Chamber of Commerce chief executive Tom Donohue in Washington DC during his St Patrick's visit to the United States.
He was speaking on Wednesday evening, Irish time, as MPs voted in Westminster against leaving the European Union on March 29 without a deal.
Yesterday, the House of Commons voted down Prime Minister Theresa May's proposed Withdrawal Deal.
Mr Varadkar said: "It's always important to remind ourselves that Brexit is not our policy...This is the decision that the UK has made, a decision that we deeply regret in Ireland and across Europe.
"If they were ever to change their mind, they would be like the prodigal son returning, and we would welcome them with open arms.
"But we have to respect the decision they have made, which is to leave.
"Whatever happens we (Ireland) made our decision a long time ago, that we're going to stay at the heart of the EU."
Mr Varadkar told an audience, which included members of the Chamber of Commerce and senior Irish executives, that Ireland and the EU wants a Brexit deal.
"We don't believe in tariffs or quotas, or differences in regulations, that's what the Customs Union and Single Market was all about getting rid of those things," he added.
"We regret that people are now suggesting we go back to that.
"I wonder whether those who advocated Brexit two or three years ago, did they really think it would be about imposing tariffs on each other and paper work and quotas, as that's where we heading if we don't have a deal."
Brexit is not our policy...This is the decision that the UK has made, a decision that we deeply regret in Ireland and across Europe.
Mr Donohue asked Mr Varadkar how his party have maintained common commitments in relation to Brexit with Fianna Fail and Sinn Fein.
"We have a consensus across the Dáil on a couple of issues and Brexit is one of those," Mr Varadkar said.
"Paramount there is protecting the peace process and the Good Friday Agreement, which has to override any economic or trade related considerations.
"We have made so much progress in the last 20 years, with the help of America, in eliminating differences between people in Northern Ireland and north and south (and) sweeping away the hard border that used to exist and we can't allow that to fall backwards.
"Even a party like Sinn Féin which used to contribute to the violence and defended some of the violence that happened 20 or 30 years ago, used to be a very anti-European party and wanted us to leave the EU until a few years ago, (but) has now abandoned their policies in those areas."
'Is this really what they wanted?'
Earlier the Taoiseach said those who advocated for Brexit have been "chasing unicorns" for a "very long time".
"As we head into the next few weeks it should be blatantly obvious that unicorns only exist in fairytales," he said.
"I would say to people who advocated Brexit - is this really what they wanted? Protectionism, borders, tariffs, restrictions on trade.
"Is this really what Brexit was all about? And for those who voted against the Withdrawal Agreement on the basis that they feared that Northern Ireland would be treated differently as a result of the backstop, it must be evident to them now that it's the UK Government's intention to treat Northern Ireland differently."
Addressing the UK's tariff proposals in the event of a no-deal Brexit, Mr Varadkar said Northern Ireland will become a back door to the European single market.
"I don't think the UK's proposals will be workable for very long. They propose to treat Northern Ireland differently from the rest of the UK," he said.
"Northern Ireland will become a back door to the European single market and I think that in a matter of months that will lead to the need for checks at Northern Ireland's ports.
"So those that opposed the agreement may find that something very akin to the backstop is applied by the UK Government in a few weeks' time."
Mr Varadkar also said that in the event of a no-deal Brexit the European customs code will apply to goods exported from the UK to the EU.
"That will obviously have a severe impact on the UK economy and the Northern Ireland economy in particular.
"Westminster can take the no-deal off the table this evening, and if they do so then there is the potential to look at alternatives, for example the UK staying in the customs union."
Mr Varadkar added that Ireland has been preparing for a no-deal Brexit scenario for a long time.
"We are well placed to deal with any shock that may arise from a no-deal (Brexit)," he added.
"The fact that we have a budget surplus means that we can borrow if we have to support our economy."