A rejection of the EU Reform Treaty could scare US boardrooms which have put €52 billion worth of investment in Ireland, Ibec said today.
Ibec, which represents 7,000 businesses, has urged a yes vote in the referendum expected in early June.
There are currently 470 US companies operating in Ireland, which provide over 95,000 high-skilled jobs.
Ibec said new research found that total US investment in Ireland is worth more than the combined US business presence in China, Russia, India and Brazil.
Ibec said the Lisbon Treaty will safeguard jobs and will better position Europe and Ireland to win more US foreign direct investment in the future.
Ibec's director of EU and international affairs Brendan Butler said: "These 470 companies that have set up here did so because of our favourable tax rates, our access to an EU market of 500 million customers and our well-educated English speaking workforce.
"A no vote would create uncertainty and send a very worrying signal back into the boardrooms of American companies, where decisions are made about future investment in Ireland."
Mr Butler said a yes vote will mean Ireland's ability to set our own tax policy is guaranteed.
"Therefore Ireland will remain among one of the most attractive places in the world to invest. The success of the Treaty will encourage more US investment and the creation of more jobs."
Ibec cited research carried out by the Centre for Transatlantic Relations at Johns Hopkins University found that US investment in Ireland is worth €52.5 billion compared to €45.6 billion in China, Russia, India and Brazil
combined.
Ibec represents businesses which make up about 70 per cent of the private sector workforce in Ireland.
PA