Ireland in crunch EU treaty vote
The No lobby has mounted a strong challenge and the result - set to be announced on Friday afternoon - could be close, judging by opinion polls.
All 27 member states have to ratify the Lisbon Treaty for it to take effect.
Constitutional changes in Ireland require a referendum. In the other 26 states parliament will decide.
All of the main Irish parties back the treaty, but many voters were undecided in the run-up.
The Lisbon Treaty replaces a more ambitious draft constitution that was rejected by French and Dutch voters in 2005.
Mark Mardell on what would sway the vote
It provides for a streamlining of the European Commission, the removal of the national veto in more policy areas, a new president of the European Council and a strengthened foreign affairs post. Fourteen countries have completed ratification so far.
The BBC's Jonny Dymond in Dublin says that a No vote could plunge the EU into crisis.
All eyes will be on the turnout - a figure below 40% would almost certainly sink the treaty, our correspondent says.
The Irish state broadcaster RTE said turnout was mixed. It was reported to be "brisk" in Kilkenny and Wicklow, but in many other areas, including Cork, Meath and Louth, it was slow.
Polling ends at 2200 (2100 GMT) and counting starts on Friday morning, with the result expected soon after 1530 (1430 GMT) on Friday.