In the frantic final round of campaigning which ended yesterday, Renzi's rivals vowed to defeat referendum proposals to streamline parliament and force the centre-left leader out of office.
The 41-year-old premier is hoping for a last-minute turnaround in voter sentiment, having pledged to quit in the event of a "No".
While all media comment on the referendum is now banned until polling ends at 11:00 pm (2200 GMT) tomorrow, the campaign continued on social media.
Politically and economically, the stakes are high.
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After Britain's vote to leave the European Union and Donald Trump's presidential triumph in the United States, Renzi is being portrayed as next in line to suffer a populist backlash from fed-up and forgotten voters.
A "No" vote would be seen as bolstering the populist Five Star Movement as well as the anti-immigrant, anti-EU Northern League.
The possibility of Renzi stepping down from power has focused the campaign on his record, exacerbating fears of political instability and economic turbulence in the eurozone's third-biggest economy should he be forced out.
At stake is whether to slash the size and powers of the second chamber Senate and transfer other powers from the regions to the national government.
Renzi says this will mean more effective leadership of a country that has had 60 governments since the constitution was approved in 1948.
And it seems certain some disgruntled voters will vote "No" as a protest -- either against Renzi or the years of economic stagnation.
Some 50 million Italians are eligible to vote, but many have yet to make up their minds.