Voting No in the referendum would damage investor confidence and put prosperity and jobs at risk, the former European Commissioner, Mr Ray MacSharry, has told a special conference on Nice organised in Dublin by the employers' group, IBEC.
He said there was an "unanswerably strong" case for a Yes vote. "The Treaty of Nice is the only agreed basis for enlargement, and a failure to ratify it would throw the whole process into confusion.
"There is nothing in the Treaty of Nice - nothing - which damages our basic interests or fundamentally changes the nature of the Union. EU membership has been positive for Ireland and it is not wise for us to change direction now."
Nobody could predict "in exact detail" the consequences of a No vote but "very many good judges" believed it would damage long-term investor confidence. "At a minimum, there is a risk - a risk which, in my view, it would be extremely unwise to take. I would not be prepared to gamble with prosperity and with jobs," Mr MacSharry said.
In an impassioned plea for a Yes vote, the president of the European Parliament, Mr Pat Cox, said there was a sense that the last campaign for Nice "ran on a flat tyre". This time pro-Nice campaigners were determined that "we can touch people" and persuade them to vote Yes.
"This is now a societal question, not a governmental question. It's not a question only for politics and politicians, it's a question about the national interest, not just a narrow sectional or political interest."
Ireland had paid a very heavy price for its "splendid isolation" in the past. "We exported our people. We broke the heart of our families. We broke the backs of our communities. We broke our own national spirit."
Then it was realised that "independence with isolation" was failing us, and "intelligent interdependence" could serve us better. "Going backwards in any degree or in any sense makes no sense."
Mr Cox continued: "Lemass and Whitaker, Lynch and Hillery, FitzGerald, Spring and Bruton and others led us from isolation to connection, led us from stagnation to opportunity, led us from a pervasive sense of failure to a more self-confident and purposeful nation."
Mr Cox concluded: "For those now saying in our politics, 'No to cuts, No to Nice', I say, 'Do not allow yourself as a voter to confuse short-term politics with the profound long-term national and personal interest.' For those who feel insecure about our future in Europe, we must say, 'Don't risk it, and the way not to risk it is by voting Yes'."
Ireland's European Commissioner, Mr David Byrne, said the proposal to reduce the size of the Commission when there were 27 member-states was made in response to concern that it would become unmanageable.
"What is important is that the Commission is allowed to play its unique role as referee. As long as it can continue to perform this role, the rare absence of an Irish Commissioner should not pose a problem," Mr Byrne said.
Responding to a query about the issue from the floor, Mr Byrne pointed out that when the time came to reduce the size of the Commission, 12 new member-states, many of them small countries, would be involved in making a unanimous decision on the issue.
The former deputy prime minister of Poland, Dr Leszek Balcerowicz; Mr Martin Jahn of the Czech trade promotion agency, Czechinvest; the Minister of State for the Environment, Mr Pat the Cope Gallagher; Mr Seán Dorgan of IDA Ireland; Prof Brigid Laffan; Ms Angela Kerins of the Disability Alliance for Europe; Dr Frank Barry of UCD and the broadcaster Brian Farrell were also among the speakers.